| 1. |
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| 2. |
- Chen, Zhi, et al.
(författare)
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Large-Area Crystalline Zeolitic Imidazolate Framework Thin Films
- 2021
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:25, s. 14124-14130
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Tidskriftsartikel (refereegranskat)abstract
- We report that continuous MOF films with highly controlled thickness (from 44 to 5100 nm) can be deposited over length scales greater than 80 centimeters by a facile, fast, and cost-effective spray-coating method. Such success relies on our discovery of unprecedented perfectly dispersed colloidal solutions consisting of amorphous MOF nanoparticles, which we adopted as precursors that readily converted to the crystalline films upon low-temperature in situ heating. The colloidal solutions allow for the fabrication of compact and uniform MOF films on a great deal of substrates such as fluorine-doped tin oxide, glass, SiO2, Al2O3, Si, Cu, and even flexible polycarbonate, widening their technological applications where substrates are essential. Despite the present work focuses on the fabrication of uniform cobalt-(2-methylimidazole)2 and zinc-(2-methylimidazole)2 films, our findings mark a great possibility in producing other high-quality MOF thin films on a large scale.
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| 3. |
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| 4. |
- Duan, Jianxin, et al.
(författare)
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Understanding the Molecular Activity of Alkaline Sphingomyelinase (NPP7) by Computer Modeling
- 2010
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 49:42, s. 9096-9105
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Tidskriftsartikel (refereegranskat)abstract
- The enzymes in the nucleotide pyrophosphatase/phosphodiesterase (NPP) family have various substrates such as nucleotides, phospholipids, and sphingolipids. The substrate specificity in relation to their structures is largely unknown because no mammalian NPP complex has been crystallized. NPP7, also called alkaline sphingomyelinase (alk-SMase), is a NPP family member that may have important implications in carcinogenesis and cholesterol absorption. The sequence of NPP7 is 36% similar to that of the closest NPP member, but NPP7 has no activity against nucleotides. In this work, we predict the three-dimensional structure of NPP7 by homology modeling using a recently crystallized NPP from bacteria. Using the model, we studied the substrate specificity of the enzyme by docking. The model generated explains the functional changes in previous mutagenesis studies and rationalizes the structural basis for the lack of activity toward nucleotides. An effort to shift the substrate specificity from sphingomyelin (SM) to nucleotide was not successful but revealed a site-directed mutation that increased activity toward SM. In conclusion, this is the first study to predict the structure of a mammalian NPP and its substrate specificity by molecular modeling. The information may be helpful in understanding the functional differences of NPP members.
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| 5. |
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| 6. |
- Lensink, Marc F., et al.
(författare)
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Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment
- 2023
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Ingår i: Proteins. - : WILEY. - 0887-3585 .- 1097-0134.
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Tidskriftsartikel (refereegranskat)abstract
- We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.
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| 7. |
- Sun, Xiao-dong, et al.
(författare)
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Implementing a novel capture and ligation probe-PCR method in mass screen and treatment to support malaria elimination efforts in the China-Myanmar border region
- 2023
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Ingår i: Malaria Journal. - : BioMed Central (BMC). - 1475-2875. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMass screening and treatment (MSAT) for malaria elimination lacks an ideal diagnostic tool to allow sensitive and affordable test of the target population in the field. This study evaluated whether Capture and Ligation Probe-PCR (CLIP-PCR) could be used in a field MSAT in Laiza City, Myanmar.MethodsOn day 0, two dried blood spots were collected from each participant. On day 1, all samples were screened for Plasmodium in a 20 m(2) laboratory with workbench, a biosafety cabinet, a refrigerator, a benchtop shaking incubator and a qPCR machine, by four technicians using CLIP-PCR with sample pooling, at a health clinic of the Chinese bordering town of Nabang. On day 2, all positives were followed up and treated.ResultsOf 15,038 persons (65% of the total population) screened, 204 (1.36%) were CLIP-PCR positives. Among them, 188, 14, and 2 were infected with Plasmodium vivax, Plasmodium falciparum, and P. vivax/P. falciparum mix, respectively. The testing capacity was 538 persons/day, with a cost of US$0.92 /person. The proportion of submicroscopic infection was 64.7%. All positive individuals received treatment within 72 h after blood collection.ConclusionUsing CLIP-PCR in MSAT in low transmission settings can support the malaria elimination efforts in the China-Myanmar border region.
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| 8. |
- Wang, Sifan, et al.
(författare)
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Fire carbon emissions over Equatorial Asia reduced by shortened dry seasons
- 2023
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Ingår i: npj Climate and Atmospheric Science. - 2397-3722. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Fire carbon emissions over Equatorial Asia (EQAS) play a critical role in the global carbon cycle. Most regional fire emissions (89.0%) occur in the dry season, but how changes in the dry-season length affect the fire emissions remains poorly understood. Here we show that, the length of the EQAS dry season has decreased significantly during 1979–2021, and the delayed dry season onset (5.4 ± 1.6 (± one standard error) days decade−1) due to increased precipitation (36.4 ± 9.1 mm decade−1) in the early dry season is the main reason. The dry season length is strongly correlated with the length of the fire season. Increased precipitation during the early dry season led to a significant reduction (May: −0.7 ± 0.4 Tg C decade−1; August: −12.9 ± 6.7 Tg C decade−1) in fire carbon emissions during the early and peak fire season. Climate models from the Coupled Model Intercomparison Project Phase 6 project a continued decline in future dry season length in EQAS under medium and high-emission scenarios, implying further reductions in fire carbon emissions.
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| 9. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Alyamani, Manar, et al.
(författare)
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Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populations
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: Alkaline sphingomyelinase (NPP7) is expressed by intestinal epithelial cells and is crucial for the digestion of dietary sphingomyelin. NPP7 also inactivates proinflammatory mediators including platelet-activating factor and lysophosphatidylcholine. The aim of this study was to examine a potential role for NPP7 in the homeostasis of the intestinal immune system. Methods: We quantified the numbers of B-lymphocytes, plasma cells, T-lymphocytes including regulatory T-lymphocytes (Tregs), natural killer cells, dendritic cells, macrophages, and neutrophils, in the small and large intestines, the mesenteric lymph nodes and the spleens of heterozygous and homozygous NPP7 knockout (KO) and wildtype (WT) mice. Tissues were examined by immunohistochemistry and stainings quantified using computerized image analysis. Results: The numbers of both small and large intestinal CD3ε+, CD4+, and CD8α+ T-lymphocytes were significantly higher in NPP7 KO compared to WT mice (with a dose-response relationship in the large intestine), whereas Treg numbers were unchanged, and dendritic cell numbers reduced. In contrast, the numbers of CD3ε+ and CD4+ T-lymphocytes in mesenteric lymph nodes were significantly reduced in NPP7 KO mice, while no differences were observed in spleens. The numbers of B-lymphocytes, plasma cells, natural killer cells, macrophages, and neutrophils were similar between genotypes. Conclusion: NPP7 contributes to the regulation of dendritic cell and T-lymphocyte numbers in mesenteric lymph nodes and both the small and large intestines, thus playing a role in the homeostasis of gut immunity. Although it is likely that the downstream effects of NPP7 activity involve the sphingomyelin metabolites ceramide and spingosine-1-phosphate, the exact mechanisms behind this regulatory function of NPP7 need to be addressed in future studies.
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| 11. |
- Andersson, David, et al.
(författare)
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Expression of Alkaline Sphingomyelinase in Yeast Cells and Anti-inflammatory Effects of the Expressed Enzyme in a Rat Colitis Model.
- 2009
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 2008:Nov 7, s. 1440-1448
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Tidskriftsartikel (refereegranskat)abstract
- Alkaline sphingomyelinase (Alk-SMase) is a key enzyme in the intestinal tract for digestion of dietary sphingomyelin (SM), which generates lipid messengers with cell-cycle regulating effects. The enzyme is significantly decreased in ulcerative colitis and colon cancer. Based on this information, we wanted to investigate whether the enzyme had preventive effects against murine colitis. We report herein a method to express a biologically active Alk-SMase from Pichia pastoris yeast cells. By using the expressed enzyme to treat a rat colitis model induced by dextran sulfate sodium, we found that intrarectal instillation of Alk-SMase once daily for 1 week significantly reduced the inflammation score and protected the colonic epithelium from inflammatory destruction. We found a tendency for decreased tumor necrosis factor (TNF)-alpha expression in the Alk-SMase-treated group. This study, for the first time, provides a method to produce the enzyme and shows the potential applicability of the enzyme in the treatment of inflammatory bowel diseases.
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| 12. |
- Andersson, David, et al.
(författare)
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Ursolic acid and other pentacyclic triterpenoids stimulate intestinal alkaline sphingomyelinase in vitro
- 2006
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Ingår i: European Journal of Lipid Science and Technology. - : Wiley. - 1438-7697 .- 1438-9312. ; 108:2, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Alkaline sphingomyelinase (alk-SMase) is an enzyme that hydrolyses sphingomyelin in a bile salt-dependent manner in the gastrointestinal tract, and has been proposed as an inhibitor of colon carcinogenesis. Ursolic acid (UA) is a plant-derived pentacyclic triterpenoid that has been shown to have anti-proliferative and apoptotic effects on HT29 human colon adenocarcinoma cells, with activation of alk-SMase as an early event. The aim of this study was to study the in vitro effects of UA and its analogues on the activity of purified rat intestinal alk-SMase. Methods: Rat intestinal alk-SMase activity was determined after incubation with UA in the presence and absence of taurocholate (TC). The effect was compared with boswellic acids, another group of pentacyclic triterpenoids. Results: UA enhanced the activity of rat intestinal alk-SMase in a dose-dependent manner, without a similar effect on bacterial neutral SMase. Four types of boswellic acid also increased the enzyme activity, with the effect of acetyl-keto-beta-boswellic acid being most potent. Activation of alk-SMase by TC; at a low concentration (0.4 mM), but not at a high concentration, was enhanced by UA. Conclusions: Ursolic acid and four types of boswellic acid, all pentacyclic triterpenoids, have a stimulatory effect on the activity of intestinal alk-SMase.
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| 13. |
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| 14. |
- Andersson, David, et al.
(författare)
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Ursolic acid inhibits the formation of aberrant crypt foci and affects colonic sphingomyelin hydrolyzing enzymes in azoxymethane-treated rats
- 2008
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 1432-1335 .- 0171-5216. ; 134:1, s. 101-107
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Tidskriftsartikel (refereegranskat)abstract
- Ursolic acid (UA) is a pentacyclic triterpenoid, with anti-cancer and anti-inflammatory properties. Sphingomyelin (SM) hydrolysis generates lipid messengers regulating cell survival. Earlier studies showed that UA has anti-proliferative and apoptotic effects on HT29 cells, accompanied by a rapid increase in alkaline sphingomyelinase (Alk-SMase) activity. This study examines the effect of orally administered UA on the formation of aberrant crypt foci (ACF) and intestinal SMase activity in azoxymethane (AOM)-treated rats. Sprague-Dawley rats were divided into eight groups, receiving AOM or vehicle, and fed normal diet or pellets containing 0.11% UA in the initiation or promotion/progression phase. The formation of ACF in the colon and the activities of three types of mucosal SMase were examined. UA significantly reduced the incidence of ACF containing three or more crypts in the initiation group, but had no significant effect in the promotion/progression group. AOM reduced mucosal Alk-SMase activity, and the inhibitory effects could not be prevented by UA. However, in both AOM-treated and normal rats, UA increased the activity of colonic neutral SMase markedly and that of acid SMase activity mildly. These results indicate that UA has chemopreventive effects in the initiation phase of colon cancer associated with changes in SM metabolism.
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| 15. |
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| 16. |
- Cárdenas, Marité, et al.
(författare)
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Solubilization of sphingomyelin vesicles by addition of a bile salt.
- 2008
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Ingår i: Chemistry and Physics of Lipids. - : Elsevier BV. - 0009-3084 .- 1873-2941. ; 151:Sep 25, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- The interactions of the bile salt sodium taurocholate (TC) in 50mM Trizma-HCl buffer and 150mM NaCl (pH 9) at 37 degrees C with membranes composed of sphingomyelin (SM) were studied by dynamic light scattering, cryogenic transmission electron microscopy (cryo-TEM) and turbidity measurements. Small unilamellar SM vesicles were prepared by extrusion. Below the CMC of TC, taurocholate addition leads to vesicle growth due to incorporation of the taurocholate molecules into the vesicle bilayer. At around half the CMC of the bile salt, the SM vesicles are transformed into SM/TC mixed worm-like micelles, which are visualized by cryo-TEM for the first time. Further increase in the taurocholate concentration leads to the rupture of these structures into small spherical micelles. Interestingly, large non-spherical micelles were also identified for pure taurocholate solutions. Similar threadlike structures have been reported earlier for the bile salt sodium taurodeoxycholate [Rich, A., Blow, D., 1958. Nature 182, 1777; Blow, D.M., Rich, A., 1960. J. Am. Chem. Soc. 82, 3566-3571; Galantini, L., Giglio, E., La Mesa, C., Viorel-Pavel, N., Punzo, F., 2002. Langmuir 18, 2812] and for mixtures of taurocholate and phosphatidylcholate [Ulmius, J., Lindblom, G., Wennerström, H., Johansson, L.B.-A., Fontel, K., Söderman, O., Ardvisson, G., 1982. Biochemistry 21, 1553; Hjelm, R.P., Thiyagarajan, P., Alkan-Onyuksel, H., 1992. J. Phys. Chem. 96, 8653] as determined by various scattering methods.
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| 17. |
- Chen, Chao, et al.
(författare)
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Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
- 2020
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 12:11, s. 10642-10662
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation-age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation-age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354PRODH, with effects significantly modified by age (HRinteraction = 0.989; 95% CI: 0.986-0.994; P = 9.18×10-7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HRyoung = 2.44; 95% CI: 1.26-4.72; P = 8.34×10-3; HRelderly = 0.58; 95% CI: 0.42-0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354PRODH methylation and elderly age (HRinteraction = 0.21; 95% CI: 0.11-0.40; P = 2.20×10-6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.
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| 18. |
- Chen, Xuan, et al.
(författare)
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Prevalence of Abdominal Obesity in Chinese Middle-Aged and Older Adults with a Normal Body Mass Index and Its Association with Type 2 Diabetes Mellitus : A Nationally Representative Cohort Study from 2011 to 2018
- 2021
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Ingår i: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. - 1178-7007. ; 14, s. 4829-4841
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies have focused on the prevalence of abdominal obesity in Chinese middle-aged and older adults with a normal body mass index (BMI). Furthermore, it is still unclear whether abdominal obesity is an independent risk factor for type 2 diabetes mellitus (T2DM). Participants with a normal BMI are usually neglected during assessments of abdominal obesity-associated T2DM risk since the current recommendations for medical interventions are mainly focused on overall body mass index rather than fat deposition patterns. Methods: In this study, 7942 normal-BMI participants aged over 45 years from the China Health and Retirement Longitudinal Study were included to assess the prevalence of abdominal obesity defined by waist circumference (WC) or waist-to-height ratio (WHtR). In addition, 4348 normal-BMI individuals with no diabetes at baseline were included to evaluate the association between abdominal obesity and the risk of T2DM with the Cox proportional hazards model. Results: The prevalence (95% confidence interval, CI) of increased WC and substantially increased WC among adults with a normal BMI was 22.0% (21.1%-22.9%) and 18.1% (17.3%-19.0%), respectively. The adjusted hazard ratios and 95% CIs for T2DM incidence were 1.39 (1.05–1.85) and 1.89 (1.42–2.53) for those with increased WC and substantially increased WC, respectively, compared to the individuals with a normal WC. Similar HRs were obtained for the association between WHtR and the risk of T2DM. In prediabetic patients, the HRs (95% CIs) for new-onset T2DM for those with increased WC and substantially increased WC were 1.85 (1.27–2.69) and 2.46 (1.67–3.61), respectively, when compared with individuals with normal WC. This positive association was observed in women but not in men or adults with normal glucose tolerance (NGT). Conclusion: Abdominal obesity is highly prevalent among middle-aged and older Chinese adults with a normal BMI, and maintaining a normal waist circumference may be beneficial in the prevention of T2DM.
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| 19. |
- Chen, Ying, et al.
(författare)
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Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice.
- 2015
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Ingår i: Molecular Cancer Therapeutics. - 1538-8514. ; 14:1, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor (PAF) and is previously suggested to have anticancer properties. The direct evidence is still lacking. We studied colonic tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced AOM/DSS method. beta-catenin was determined by immunohistochemistry, PAF levels by ELISA and sphingomyelin metabolites by mass spectrometry. Without treatment, spontaneous tumorigenesis was not identified but the intestinal mucosa appeared thicker in KO than in wild type (WT) littermates. AOM alone induced more ACF in KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS treatments induced colonic tumors and the incidence was significantly higher in KO than in WT mice. By the enhanced AOM/DSS method tumor number per mouse increased 4.5 times and tumor size 1.8 times in KO compared to WT mice. While all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO mice. Compared to WT mice, cytosol expression of beta-catenin was significantly decreased and nuclear translocation in tumors was more pronounced in KO mice. Lipid analysis showed decreased ceramide in small intestine and increased sphingosine-1-phosphate in both small intestine and colon in nontreated KO mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS treatment. In conclusion lack of alk-SMase markedly increases AOM/DSS induced colonic tumorigenesis associated with decreased ceramide and increased sphingosine-1-phosphate and PAF levels.
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| 20. |
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| 21. |
- Cheng, Yajun, et al.
(författare)
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Curcumin decreases acid sphingomyelinase activity in colon cancer caco-2 cells
- 2007
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Ingår i: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 73:8, s. 725-730
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Tidskriftsartikel (refereegranskat)abstract
- Curcumin has been shown to inhibit cell growth and induce apoptosis in colon cancer cells. The metabolism of sphingomyelin has implications in the development of colon cancer. We examined whether curcumin affects the enzymes that hydrolyse sphingomyelin in Caco-2 cells. The cells were cultured in both monolayer and polarized conditions and stimulated with curcumin. The activities of sphingomyelinases were determined. Sphingomyelin and its hydrolytic products were analysed by thin layer chromatography. The changes of acid sphingomyelinase protein were examined by Western blotting. We found that curcumin reduced the hydrolytic capacity of the cells against choline-labelled sphingomyelin, associated with a mild increase of cellular sphingomyelin in the cells. Analysis of the hydrolytic products revealed that the activity was derived from acid sphingomyelinase not from phospholipase D. The curcumin-induced reduction of acid SMase required more than 8 h stimulation. Western blotting showed reduced acid sphingomyelinase protein after curcumin stimulation. The inhibitory effect was more potent in monolayer cells than in polarised cells. No changes of other sphingomyelinases were identified. In the concentrations inhibiting acid sphingomyelinase, curcumin inhibited DNA synthesis and induced cell death. In conclusion, curcumin inhibits acid sphingomyelinase and the effect might be involved in its anti proliferative property against colon cancer cells.
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| 22. |
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| 23. |
- Cheng, Yajun, et al.
(författare)
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Ezetimibe Inhibits Expression of Acid Sphingomyelinase in Liver and Intestine.
- 2009
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Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 44:10, s. 897-906
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Tidskriftsartikel (refereegranskat)abstract
- Ezetimibe inhibits cholesterol absorption in the intestine. Sphingomyelin has strong interactions with cholesterol. We investigated the effects of ezetimibe on Sphingomyelinase (SMase) expression in intestine and liver. After feeding rats with ezetimibe (5 mg/kg per day) for 14 days, acid SMase activities in the liver and in the proximal part of small intestine were reduced by 34 and 25%, respectively. Alkaline SMase (alk-SMase) was increased in the proximal part of the small intestine. Administration of lower doses of ezetimibe reduced acid SMase only in the liver by 14% (P < 0.05). In cell culture studies, ezetimibe decreased acid SMase activity in Hep G2 and Caco-2 cells dose-dependently. The reductions were more rapid for Hep G2 cells than for Caco-2 cells. Western blot showed that acid SMase protein was decreased in both Hep G2 and Caco-2 cells by 100 muM ezetimibe. The SM content was increased in Hep G2 cells but not Caco-2 cells, and total cholesterol content was increased in both cell lines 24 h after stimulation with 100 muM ezetimibe. Mevastatin, the inhibitor of cholesterol synthesis, induced a mild increase in acid SMase activity in Hep G2 cells but not Caco-2 cells. Following the reduction of acid SMase, ezetimibe at high dose slightly increased alk-SMase activity. In conclusion, the study demonstrates an inhibitory effect of ezetimibe on acid SMase activity and expression in both liver and intestine.
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| 24. |
- Cheng, Yajun, et al.
(författare)
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Psyllium and fat in diets differentially affect the activities and expressions of colonic sphingomyelinases and caspase in mice.
- 2004
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 91:5, s. 715-723
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Tidskriftsartikel (refereegranskat)abstract
- Dietary fibre and fat affect colonic tumourigenesis and inflammation. Sphingomyelin metabolism may have implications for the pathogenesis of colonic tumours and ulcerative colitis. The present study examined the effects of psyllium and fat on the enzymes responsible for sphingomyelin metabolism and apoptosis in the colon. Mice were fed control, psyllium-containing (100 g/kg), high-fat (313 g/kg, 53 % energy as fat) or high-fat plus psyllium diets for 4 weeks. The activities of acid, neutral and alkaline sphingomyelinase (SMase), neutral ceramidase, and caspase 3, 8 and 9 in colonic mucosa were determined. The expressions of alkaline SMase and caspase 3 were examined. The psyllium-containing diet was found to increase significantly the activities of alkaline SMase and caspase 3 and decreased those of acid SMase and neutral ceramidase. The high-fat diet had opposite effects on these enzymes and attenuated the effects of psyllium. Western blotting showed that psyllium increased and high-fat decreased the levels of alkaline SMase and caspase 3 in colonic mucosa. The change in caspase 3 activity was positively correlated with that of alkaline SMase and negatively with acid SMase. No similar changes of acid and alkaline phosphatase activities in the colon or acid and neutral SMase activity in the liver were identified. In conclusion, colonic sphingomyelin metabolism and apoptosis were affected by psyllium and fat in an opposite manner. The results may have implications for colorectal tumourigenesis and inflammation.
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| 25. |
- Cheng, Yajun, et al.
(författare)
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Purification, characterization, and expression of rat intestinal alkaline sphingomyelinase.
- 2002
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Ingår i: Journal of Lipid Research. - 1539-7262. ; 43:2, s. 316-324
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal alkaline sphingomyelinase (SMase) has physiological roles in the digestion of sphingomyelin (SM) and clinical implications in colonic carcinogenesis. In the present work, the enzyme from rat has been purified 1,589-fold with 11% recovery by elution of the intestine with bile salt, precipitation of the proteins by acetone, and several types of chromatographies. Its molecular mass was 58 kDa and optimal pH was 9 to 9.5. Under the optimal conditions, the V(max) was 930 micromol/h/mg and K(m) was about 1.25 mM. The enzyme could hydrolyze phosphatidylcholine at pH 7.4 in the presence of Ca2+; the rate was about 8% of that for SM. The activity against SM was dependent on bile salt. Taurine conjugated bile salts were much more effective than glycine conjugated ones, and the most effective bile salts were taurocholate and taurochenodeoxycholate. 3-[(3-Cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) and Triton X100 (TX100) had no stimulatory effects. Unlike neutral SMase, intestinal alkaline SMase was not Mg2+ dependent, not inhibited by EDTA, and not inhibited by glutathione. The enzyme was stable during incubation with temperatures up to 50 degree C and in pHs from 7 to 10. Trypsin and chymotrypsin had no effects on its activity, and 10 mM dithiothreitol reduced its activity by 25%. A specific antibody against the enzyme was developed, and Western blot showed that the enzyme was expressed in the intestine but not in other organs. In conclusion, we purified a potentially important SMase in the intestine with several properties different from neutral SMase.
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| 26. |
- Dong, Xuesi, et al.
(författare)
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Trans-omics biomarker model improves prognostic prediction accuracy for early-stage lung adenocarcinoma
- 2019
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:16, s. 6312-6335
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Tidskriftsartikel (refereegranskat)abstract
- Limited studies have focused on developing prognostic models with trans-omics biomarkers for early-stage lung adenocarcinoma (LUAD). We performed integrative analysis of clinical information, DNA methylation, and gene expression data using 825 early-stage LUAD patients from 5 cohorts. Ranger algorithm was used to screen prognosis-associated biomarkers, which were confirmed with a validation phase. Clinical and biomarker information was fused using an iCluster plus algorithm, which significantly distinguished patients into high- and low-mortality risk groups (Pdiscovery = 0.01 and Pvalidation = 2.71×10-3). Further, potential functional DNA methylation-gene expression-overall survival pathways were evaluated by causal mediation analysis. The effect of DNA methylation level on LUAD survival was significantly mediated through gene expression level. By adding DNA methylation and gene expression biomarkers to a model of only clinical data, the AUCs of the trans-omics model improved by 18.3% (to 87.2%) and 16.4% (to 85.3%) in discovery and validation phases, respectively. Further, concordance index of the nomogram was 0.81 and 0.77 in discovery and validation phases, respectively. Based on systematic review of published literatures, our model was superior to all existing models for early-stage LUAD. In summary, our trans-omics model may help physicians accurately identify patients with high mortality risk.
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| 27. |
- Duan, Ming-Rui, et al.
(författare)
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DNA binding mechanism revealed by high resolution crystal structure of Arabidopsis thaliana WRKY1 protein
- 2007
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 35:4, s. 54-1145
-
Tidskriftsartikel (refereegranskat)abstract
- WRKY proteins, defined by the conserved WRKYGQK sequence, are comprised of a large superfamily of transcription factors identified specifically from the plant kingdom. This superfamily plays important roles in plant disease resistance, abiotic stress, senescence as well as in some developmental processes. In this study, the Arabidopsis WRKY1 was shown to be involved in the salicylic acid signaling pathway and partially dependent on NPR1; a C-terminal domain of WRKY1, AtWRKY1-C, was constructed for structural studies. Previous investigations showed that DNA binding of the WRKY proteins was localized at the WRKY domains and these domains may define novel zinc-binding motifs. The crystal structure of the AtWRKY1-C determined at 1.6 A resolution has revealed that this domain is composed of a globular structure with five beta strands, forming an antiparallel beta-sheet. A novel zinc-binding site is situated at one end of the beta-sheet, between strands beta4 and beta5. Based on this high-resolution crystal structure and site-directed mutagenesis, we have defined and confirmed that the DNA-binding residues of AtWRKY1-C are located at beta2 and beta3 strands. These results provided us with structural information to understand the mechanism of transcriptional control and signal transduction events of the WRKY proteins.
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| 28. |
- Duan, Rui-Dong
(författare)
-
Alkaline sphingomyelinase: An old enzyme with novel implications.
- 2006
-
Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1761:3, s. 281-291
-
Forskningsöversikt (refereegranskat)abstract
- Alkaline sphingomyelinase (alk-SMase) is present in the intestinal tract and additionally human bile. It hydrolyses sphingomyelin in both intestinal lumen and the mucosal membrane in a specific bile salt dependent manner. The enzyme was discovered 36 years ago but got real attention only in the last decade, when sphingomyelin metabolism was realized to be a source of multiple lipid messengers, and when dietary sphingomyelin was found to inhibit colonic tumorigenesis in animals. The enzyme shares no structural similarity with other SMases and belongs to the nucleotide pyrophosphatase/phosphodiesterase family. The enzyme is of specific properties, such as bile salt dependency, trypsin resistance, high stability, and tissue specific expression. In the colon, the enzyme may play antiproliferative and antiinflammatory roles through generating ceramide, reducing the formation of lysophosphatidic acid, and inactivating platelet-activating factor. The enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma, and mutation of the enzyme has been found in colon cancer cells. In the small intestine, alk-SMase is the key enzyme for sphingomyelin digestion. The hydrolysis of sphingomyelin may affect the cholesterol uptake and have impact on sphingomyelin levels in plasma lipoproteins. The review summarizes the new information of alk-SMase from biochemical, cell and molecular biological studies in the last decade and evaluates its potential implications in development of colon cancer, inflammatory bowel diseases, and atherosclerosis. (c) 2006 Elsevier B.V. All rights reserved.
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| 29. |
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| 30. |
- Duan, Rui Dong
(författare)
-
Alkaline sphingomyelinase (NPP7) in hepatobiliary diseases : A field that needs to be closely studied
- 2018
-
Ingår i: World Journal of Hepatology. - : Baishideng Publishing Group Inc.. - 1948-5182. ; 10:2, s. 246-253
-
Forskningsöversikt (refereegranskat)abstract
- Alkaline sphingomyelinase cleaves phosphocholine from sphingomyelin, platelet-activating factor, lysophosphatidylcholine, and less effectively phosphatidylcholine The enzyme shares no structure similarities with acid or neutral sphingomyelinase but belongs to ectonucleotide pyrophosphatase/phosphodiesterase (NPP) family and therefore is also called NPP7 nowadays. The enzyme is expressed in the intestinal mucosa in many species and additionally in human liver. The enzyme in the intestinal tract has been extensively studied but not that in human liver. Studies on intestinal alkaline sphingomyelinase show that it inhibits colonic tumorigenesis and inflammation, hydrolyses dietary sphingomyelin, and stimulates cholesterol absorption. The review aims to summarize the current knowledge on liver alkaline sphingomyelinase in human and strengthen the necessity for close study on this unique human enzyme in hepatobiliary diseases.
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| 31. |
- Duan, Rui-Dong, et al.
(författare)
-
Alkaliskt sfingomyelinas, en antiinflamatorisk faktor som kan motverka colit och colorektal cancer
- 2019
-
Ingår i: Gastrokuriren. - 1651-0453. ; 24:2, s. 26-27
-
Konferensbidrag (refereegranskat)abstract
- Alkaliskt sfingomyelinas, en antiinflammatorisk faktor som kan motverka colit och colorektal cancer Rui-Dong Duan, Erik Hertervig, Åke NilssonBakgrund: Borstbrämsenzymet alkaliskt sfingomyelinas (alk-SMas) som vi upptäckt, renat och klonat hydrolyserar sfingomyelin (SM) och den proinflammatoriska glycerofosfolipiden platelet activating factor (PAF). Metaboliter av SM är anticarcinogena och inaktivering av PAF är antiinflammatorisk. Alk-SMas nivån är sänkt vid coloncancer (CRC) (1), familjär colonpolypos och långvarig colit. Rektal administration av rekombinant alk-SMas lindrar experimentell colit och alk-SMas knockout (KO) möss är känsligare för induktion av colontumörer i en kombinerad colit/carcinogenmodell (2). Enzymet secerneras också i human galla och vi fann låga värden i ERCP galla från patienter med PSC och cholangiocarcinom. Alk-SMas KO möss utvecklar svårare dextransulfat colit än kontrollmöss (3). Metod: Vi analyserade PAF, enzymet autotaxin och dess metabolit lysofosfatidinsyra (LPA) i mucosan hos alk-SMas KO och kontrolldjur med colit inducerad med dextransulfat (3). Både PAF och LPA är trofiska och proinflammatoriska signalsubstanser. Fynden relaterades till colitens svårighetsgrad. Studien gav en mekanistisk bakgrund till alk-SMas anticarcinogena och antiinflammatoriska effekter. Vi kan därigenom bättre bedöma alk-SMas kliniska potential. Resultat: Vi fann att alk-SMas KO möss har högre PAF nivåer i mucosan under colitens induktionsfas och att nivån av autotaxin och LPA är högre i KO djuren när inflammationen etablerats (3). Bland våra tidigare fynd vill vi lyfta fram att alk-SMas uttryck kan nedregleras av fettrik kost, och ökas av lösliga fiber, 5-ASA och ursodeoxycholsyra. Slutsats: 1. Den anticarcinogena effekten av alk-SMas kan vara sekundär till den antiinflammatoriska effekten. 2. Reduktionen av på PAF och LPA nivåer är sannolikt viktigare för effekten än bildningen av sfingolipidmetaboliter. 3. Påverkan på alk-SMas nivån bidrar till kända effekter av kost och farmaka på inflammation och carcinogenes i colon. 4. Alk-SMas är proteasresistent och kan analyseras i faeces. 5 Alk SMase kan ges som slow release eller rektal beredning. Referenser: 1.Hertervig E, Nilsson A, Nyberg L, Duan RD. Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma. Cancer. 1997; 79:448-53. 2. Chen Y, Zhang P, Xu SC, Yang L, Voss U, Ekblad E, Wu Y, Min Y, Hertervig E, Nilsson Å, Duan RD. Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice. Mol Cancer Ther. 2015; 14:259-67.3. Zhang P, Chen Y, Zhang T, Zhu J, Zhao L, Li J, Wang G, Li Y, Xu S, Nilsson Å, Duan RD. Deficiency of alkaline SMase enhances dextran sulfate-induced colitis in mice with upregulation of autotaxin. J Lipid Res. 2018; 59:1841-1850.
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| 32. |
- Duan, Rui-Dong, et al.
(författare)
-
Altered synthesis of some secretory proteins in pancreatic lobules isolated from streptozotocin-induced diabetic rats
- 1990
-
Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:2, s. 136-143
-
Tidskriftsartikel (refereegranskat)abstract
- The in vitro incorporation of [35S]cysteine into lipase, colipase, amylase, procarboxypeptidase A and B, and the serine proteases and total proteins was studied in pancreatic lobules isolated from normal and diabetic rats with or without insulin treatment. The incorporation of [35S]cysteine into total proteins was 65% greater in pancreatic lobules from diabetic animals than from normal rats. The increased incorporation was partly reversed by insulin treatment (2 U/100 g/day for 5 days) of diabetic rats. The relative rates of biosynthesis for amylase and the procarboxypeptidases in diabetic pancreatic lobules were decreased by 75 and 25%, respectively, after 1 h of incubation, while those for lipase, colipase, and the serine proteases were increased by 90, 85, and 35%, respectively. The absolute rates of synthesis for these enzymes changed in the same direction as the relative rates in diabetic lobules, except that for the procarboxypeptidases, which did not change. The changed rates of biosynthesis for the pancreatic enzymes were reversed by insulin treatment of the diabetic rats. Kinetic studies showed that the incorporation of [35S]cysteine into amylase, lipase, and colipase was linear until up to 2 h of incubation in normal pancreatic lobules, while in the diabetic lobules the incorporation into lipase and colipase was accelerated, reaching a plateau level already after 1 h of incubation. It is concluded that the biosynthesis of pancreatic secretory proteins in diabetic rats is greatly changed both in terms of quantity and kinetics.
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| 33. |
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| 34. |
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| 35. |
- Duan, Rui-Dong, et al.
(författare)
-
Changes of activity and isoforms of alkaline sphingomyelinase (nucleotide pyrophosphatase phosphodiesterase 7) in bile from patients undergoing endoscopic retrograde cholangiopancreatography.
- 2014
-
Ingår i: BMC Gastroenterology. - 1471-230X. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Alkaline sphingomyelinase (NPP7) is an ecto-enzyme expressed in intestinal mucosa, which hydrolyses sphingomyelin (SM) to ceramide and inactivates platelet activating factor. It is also expressed in human liver and released in the bile. The enzyme may have anti-tumour and anti-inflammatory effects in colon and its levels are decreased in patients with colon cancer and ulcerative colitis. Active NPP7 is translated from a transcript of 1.4 kb, whereas an inactive form from a 1.2 kb mRNA was found in colon and liver cancer cell lines. While the roles of NPP7 in colon cancer have been intensively studied, less is known about the function and implications of NPP7 in the bile. The present study examines the changes of NPP7 in bile of patients with various hepatobiliary diseases.
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| 36. |
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| 37. |
- Duan, Rui-Dong, et al.
(författare)
-
Decrease in contents of pancreatic carboxyl ester lipase, phospholipase A2 and lingual lipase in rats with with streptozotocin-induced diabetes.
- 1993
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 28:3, s. 256-260
-
Tidskriftsartikel (refereegranskat)abstract
- The changes in contents of pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase in rats with streptozotocin (STZ)-induced diabetes have been studied. The contents of pancreatic carboxyl ester lipase and phospholipase A2 decreased by 40% and 45%, respectively, 5 days after injection of STZ, whereas pancreatic lipase steadily increased to 100% over control. The content of lingual lipase decreased sharply by more than 90% 2 days after STZ injection, followed by a tendency to recover slightly. Insulin treatment at a dose abolishing the urine glucose in diabetic rats for 3 days restored the contents of pancreatic lipase, carboxyl ester lipase, and lingual lipase but not pancreatic phospholipase A2. The results indicate that lack of insulin action induces an anticoordinate change in gastrointestinal lipolytic enzymes, with decreases in pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase contents and an increase in pancreatic lipase content.
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| 38. |
- Duan, Rui-Dong, et al.
(författare)
-
Effect of emeriamine on exocrine and endocrine pancreatic function in normal and diabetic rats
- 1992
-
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 52:7, s. 579-584
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of emeriamine, a new anti-diabetic drug, on exocrine and endocrine pancreatic function in normal and diabetic rats have been studied both in vivo and in vitro. It was found that emeriamine dose-dependently normalized the symptoms of hyperingestion and hyperposia in streptozotocin (STZ)-induced diabetic rats, with fasting glucose levels significantly decreased and insulin levels not changed. In STZ-induced diabetic rats, there was a significant increase in pancreatic lipase and trypsin contents and a sharp decrease in amylase content. These changes in lipase and trypsin, but not in amylase were normalized by administration of emeriamine. In the normal rat, emeriamine had no effect on either serum glucose or insulin levels, but significantly decreased the pancreatic amylase, lipase as well as trypsin contents by 68%, 58% and 51%, respectively. In vitro, emeriamine (10−8-10−4 mol l−1) had no effect on enzyme release from pancreatic acini either under basal or carbachol-stimulated conditions. Emeriamine inhibited glucose-induced insulin release from isolated pancreatic islets. In conclusion, emeriamine has an inhibitory effect on synthesis of pancreatic enzymes and on glucose-stimulated insulin release.
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| 39. |
- Duan, Rui-Dong, et al.
(författare)
-
Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase.
- 2007
-
Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1771:2, s. 196-201
-
Tidskriftsartikel (refereegranskat)abstract
- Alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase (N-CDase) in the intestinal microvillar membrane are responsible for dietary sphingomyelin digestion. The activities of the enzymes require the presence of bile salt, and the enzymes can be released into the gut lumen in active forms by bile salts and trypsin. It is unclear to what extent that the intestinal presence of bile salts is critical for the intraluminal activity of these enzymes. We compared the activities of Alk-SMase, N-CDase, and other types of SMases in control and permanently bile diverted rats. In the intestinal tract of control rats, the activity of Alk-SMase was profoundly higher than those of acid and neutral Wases. Bile diversion reduced Alk-SMase activity by 85% in the small intestinal content, and by 68% in the faeces, but did not significantly change the activity in the intestinal mucosa. Western blot showed a marked reduction of the enzyme in the intestinal lumen but not mucosa. N-CDase activities both in the intestinal mucosa and content were reduced by bile diversion. Bile diversion also decreased aminopeptidase N activity in the content and increased that in the mucosa, but had no effects on that of alkaline phosphatase. In conclusion, the presence of bile salts is important for maintaining high intraluminal levels of Alk-SMase and N-CDase, two key enzymes for hydrolysis of sphingomyelin in the gut. We speculate that the sphingomyelin hydrolysis in cholestatic conditions is impaired not only by reduced hydrolytic activity but also by deficient dissociation of the enzymes from the membrane.
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| 40. |
- Duan, Rui-Dong, et al.
(författare)
-
Effects of extracellular calcium and magnesium on bile salt stimulated amylase release from rat pancreatic acini
- 1986
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 21:10, s. 1211-1216
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of extracellular calcium and magnesium on bile-salt-induced amylase release from rat pancreatic acini have been studied. The amylase releases caused by from 0.25 mM to 1.0 mM taurodeoxycholate (TDC) and by taurochenodeoxycholate (TCDC) at a concentration of more than 0.75 mM were reduced by ethylenediaminetetraacetic acid (EDTA) and increased by verapamil. EDTA and verapamil had no significant effect on the taurocholate (TC) (1.0-5.0 mM)-stimulated amylase release. The inhibiting effect of EDTA began to appear already during the initial 5 min and was not parallel to any change of lactate dehydrogenase release. The TDC- and TCDC-stimulated amylase release was strongly dependent on the concentrations of extracellular calcium and was only weakly dependent on extracellular magnesium. The TC-induced amylase release was slightly increased only at high concentrations of calcium and magnesium. It is suggested that the mechanism of dihydroxy bile-salt-induced amylase release from rat pancreatic acini is different from that of trihydroxy bile salt. The dihydroxy bile-salt-stimulated amylase release is dependent on extracellular calcium but does not seem to be related to the uptake of calcium by the acini.
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| 41. |
- Duan, Rui-Dong, et al.
(författare)
-
Effects of verapamil on amylase release from rat pancreatic acini and its relation to calcium fluxes.
- 1988
-
Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 3:4, s. 427-432
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of verapamil on amylase release and Ca2+ fluxes from rat pancreatic acini have been studied. Verapamil at concentrations above 10 FM dose-dependently inhibited amylase release stimulated by carbachol, but enhanced the amylase release stimulated by cholecystokinin (CCK) and secretin. Verapamil had no significant effect on calcium uptake induced by carbachol or CCK, but significantly inhibited Caf2 eflux caused by carbachol and slightly increased that caused by CCK. In a Ca2+-free, EDTA-containing medium, the increase in cytoplasmic free Ca2+ caused by carbachol was significantly inhibited by verapamil. Verapamil alone up to 400 p, M had no effect on the release of lactic dehydrogenase. In conclusion, the effect of verapamil on amylase release from rat pancreatic acini differs depending on the type of secretagogue used to stimulate amylase release. This effect is not related to blockage of Ca2+ uptake, indicating another mechanism of verapamil on pancreatic acini.
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| 42. |
- Duan, Rui-Dong, et al.
(författare)
-
Evidence for specific ceramidase present in the intestinal contents of rats and humans.
- 2001
-
Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 36:8, s. 807-812
-
Tidskriftsartikel (refereegranskat)abstract
- A neutral ceramidase activity stimulated by bile salt was previously identified in the intestinal content. Recently, bile salt stimulated lipase (BSSL) was found to have ceramidase activity. It is unknown whether the ceramidase activity previously found is attributable to BSSL. To address this question, we compared the behaviors of high quaternary aminoethyl (HQ) anion exchange chromatography, the distributions, the stability, and the responses to lipase inhibitor between ceramidase and pancreatic BSSL. The proteins from whole small intestinal contents of humans and rats were precipitated by acetone and dissolved in 20 mM Tris buffer pH 8.2. These proteins had neutral ceramidase activity but not BSSL activity against p‐nitrophenyl acetate. When the proteins were subject to HQ chromatography, two peaks of ceramidase activity were identified, which had acid and neutral pH optima, respectively. Neither of them had BSSL activity against p‐nitrophenyl acetate. Western blot using BSSL antiserum failed to identify BSSL protein in the fractions, with high neutral ceramidase activity. In rat intestinal tract, pancreatic BSSL activity was high in the duodenum and declined rapidly in the small intestine, whereas neutral ceramidase activity was low in the duodenum and maintained a high level until the distal part of the small intestine. In addition, orlistat, the inhibitor of lipase, abolished human BSSL activity against p‐nitrophenyl acetate and slightly reduced its activity against ceramide but had no inhibitory effect on ceramidase activity isolated by HQ chromatography. In conclusion, we provide the evidence for a specific ceramidase other than pancreatic BSSL present in the intestinal content. The enzyme may play important roles in digestion of dietary sphingolipids.
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| 43. |
- Duan, Rui-Dong, et al.
(författare)
-
Evidence of a stimulatory effect of cyclic AMP on pancreatic lipase and colipase synthesis in rats.
- 1992
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 27:8, s. 644-648
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of endogenous and exogenous cyclic AMP on the synthesis of pancreatic lipase, colipase, and amylase were studied. Pancreatic lobules were prepared and incubated with forskolin, dibutyryl cyclic AMP (dbcAMP), and dibutyryl cyclic GMP (dbcGMP), respectively, in the presence of “S-cysteine”. The individual pancreatic enzymes were isolated by polyacrylamide gel electrophoresis, and the incorporation of radioactive cysteine into lipase, colipase, and amylase was determined. Incubation with forskolin (25 uM) rapidly increased lipase synthesis rate within 30 min, followed by an increase in colipase synthesis rate after 60 min of incubation. Amylase synthesis rate did not change during the 1st h of incubation but decreased slightly when incubated for 2h. Incubation of pancreatic lobules with dbcAMP (1 mM) for 1 h also stimulated the incorporation of cysteine into lipase and colipase by 21% and 25%, respectively, whereas incubation with dbcGMP had no effect on the synthesis rates of lipase and colipase. Neither dbcAMP nor dbcGMP had any effect on synthesis rate of amylase. It is concluded that cyclic AMP might be an important intracellular signal for the synthesis of pancreatic lipase and colipase in the rat
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| 44. |
- Duan, Rui-Dong, et al.
(författare)
-
Gastric inhibitory polypeptide stimulates synthesis of pancreatic lipase and colipase in rat.
- 1992
-
Ingår i: American Journal of Physiology: Gastrointestinal and Liver Physiology. - 1522-1547. ; 262:5 Pt 1, s. 779-784
-
Tidskriftsartikel (refereegranskat)abstract
- Effects of short-term infusion and long-term injection of gastric inhibitory polypeptide (GIP) on changes in pancreatic lipase and colipase contents in rats were studied, and mRNAs encoding for lipase and colipase were determined by Northern blot hybridization with specific cDNA probes. GIP infused at a dose of 3 micrograms/h for 24 h significantly increased the pancreatic lipase content by 34% (P less than 0.05) but had no significant effect on colipase and amylase contents. No change in mRNAs encoding for these proteins was found after infusion of GIP for 24 h. Injection of GIP (5-60 micrograms/kg) three times a day for 5 days dose dependently increased the contents of lipase and colipase, with the increase in colipase being more prominent. Injection of GIP for 5 days at a dose of 30 micrograms.kg-1.day-1 increased colipase and lipase contents by 52 and 25%, and their corresponding mRNAs by 60 and 160%, respectively. The amylase mRNA was not changed by injection of GIP. It is concluded that GIP has a specific stimulatory effect on the synthesis of pancreatic lipase and colipase at both pretranslational and translational levels.
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| 45. |
- Duan, Rui-Dong, et al.
(författare)
-
Human meconium contains significant amounts of alkaline sphingomyelinase, neutral ceramidase, and sphingolipid metabolites.
- 2007
-
Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 61:1, s. 61-66
-
Tidskriftsartikel (refereegranskat)abstract
- Intestinal alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase may catalyze the hydrolysis of endogenous sphin-gomyelin (SM) and milk SM in human-milk fed infants. The enzymes generate sphingolipid metabolites that may influence gut maturation. Alk-SMase also inactivates platelet-activating factor (PAF) that is involved in the pathogenesis of necrotizing enterocolitis (NEC). We examined whether the two enzymes are expressed in both preterm and term infants and analyzed Alk-SMase, neutral ceramidase, SM, and sphingolipid metabolites in meconium. Meconium was collected from 46 preterm (gestational ages 23-36 wk) and 38 term infants (gestational ages 37-42 wk) and analyzed for Alk-SMase using C-14-choline-labeled SM and for neutral ceramidase using C-14-octanoyl-sphingosine as substrates. Molecular species of SM, ceramide, and sphingosine were analyzed by high-performance liquid chromatography mass spectroscopy. Meconium contained significant levels of Alk-SMase and ceramidase at all gestational ages. It also contained 16-24 carbon molecular species of SM, palmitoyl-and stearoyl-sphingosine, and sphingosine. There were positive correlations between levels of SM and ceramide and between ceramide and sphingosine levels. In conclusion, Alk-SMase and ceramidase are expressed in the gut of both preterm and term newborn infants and may generate bioactive sphingolipid messengers.
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| 46. |
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| 47. |
- Duan, Rui-Dong, et al.
(författare)
-
Is there a specific lysophospholipase in human pancreatic juice?
- 1993
-
Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002. ; 1167:3, s. 326-330
-
Tidskriftsartikel (refereegranskat)abstract
- The existence of a specific lysophospholipase in human pancreatic juice was evaluated. The proteins were separated by a series of chromatographic steps including Sephacryl S-200, cholate-Sepharose 4B, Sephadex G-100 and CM-Sephadex G-50. The enzyme activities against 1-palmitoyl lysolecithin (LL) as well as tributyrin (TB) and p-nitrophenyl butyrate (PNPB) were determined in all the fractions of these purification procedures. Enzyme activity against LL was always eluted in parallel with activities against TB and PNPB, and no unique activity against LL could be found. The specific activity against LL was 40-times lower than that against PNPB and 200-times lower than that against TB. It is concluded that there is no unique lysophospholipase in human pancreatic juice and that the hydrolysis of lysolecithin is most likely performed by carboxyl ester lipase.
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| 48. |
- Duan, Rui-Dong, et al.
(författare)
-
Metabolism of sphingolipids in the gut and its relation to inflammation and cancer development.
- 2009
-
Ingår i: Progress in lipid research. - : Elsevier BV. - 1873-2194 .- 0163-7827. ; 48:1, s. 62-72
-
Tidskriftsartikel (refereegranskat)abstract
- Sphingolipids are abundant in the microvillar membrane of intestinal epithelial cells where they are essential for structural integrity and may act as receptors for toxins, virus and bacteria. Metabolism of dietary and membrane sphingolipids in the intestine generates ceramide, sphingosine, sphingosine-1-phosphate, and ceramide-1-phosphate, via the action of alkaline sphingomyelinase, neutral ceramidase, sphingosine-1-kinase, and ceramide-1-kinase. These intermediary metabolites act as bioactive lipid messengers, influencing numerous cellular functions including growth, differentiation and apoptosis of both epithelial and immunocompetent cells in the gastrointestinal tract, and also the progress of inflammation and responsiveness of the mucosal cells to pathogens. This review summarizes background and recent progress in the metabolism of dietary and endogenous sphingolipids in the gut and its pathophysiological implications.
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| 49. |
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| 50. |
- Duan, Rui-Dong
(författare)
-
Phospholipid signals and intestinal carcinogenesis
- 2006
-
Ingår i: Scandinavian Journal of Food and Nutrition. - : Informa UK Limited. - 1748-2976 .- 1748-2984. ; 50:S2, s. 45-53
-
Tidskriftsartikel (refereegranskat)abstract
- Phospholipids are an important constituent of the cell plasma membrane and are also present in most common dietary products, being particularly abundant in milk, egg, meat and beans. Phospholipids are hydrolysed by different phospholipases to generate multiple breakdown products that affect the fate of the cells. Most phospholipids such as phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol and platelet activating factor are important for cell survival and thus may promote tumorigenesis and inflammation. Sphingomyelin is unique in the sense that its hydrolysis by sphingomyelinase and ceramidase generates several lipid messengers such as ceramide and sphingosine that inhibit cell proliferation and induce apoptosis. In the intestinal tract there is a specific type of sphingomyelinase called alkaline sphingomyelinase, which can hydrolyse sphingomyelin in both the cell membrane and the diet. The enzyme may play important roles in preventing colon cancer development and inflammation by hydrolysing sphingomyelin to generate anticancer molecules, and by counteracting the cancer-promoting effects of other phospholipids such as lysophosphatidylcholine and platelet activating factor. This mini-review highlights the signal transduction pathways activated by different phospholipids, with special attention being paid to potential implications in the development of colon cancer.
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