| 1. |
- An, Xiaojin, et al.
(författare)
-
Response gene to complement 32, a novel hypoxia-regulated angiogenic inhibitor.
- 2009
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 120:7, s. 617-27
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Response gene to complement 32 (RGC-32) is induced by activation of complement and regulates cell proliferation. To determine the mechanism of RGC-32 in angiogenesis, we examined the role of RGC-32 in hypoxia-related endothelial cell function.METHODS AND RESULTS: Hypoxia/ischemia is able to stimulate both angiogenesis and apoptosis. Hypoxia-inducible factor-1/vascular endothelial growth factor is a key transcriptional regulatory pathway for angiogenesis during hypoxia. We demonstrated that the increased RGC-32 expression by hypoxia was via hypoxia-inducible factor-1/vascular endothelial growth factor induction in cultured endothelial cells. However, overexpression of RGC-32 reduced the proliferation and migration and destabilized vascular structure formation in vitro and inhibited angiogenesis in Matrigel assays in vivo. Silencing RGC-32 had an opposing, stimulatory effect. RGC-32 also stimulated apoptosis as shown by the increased apoptotic cells and caspase-3 cleavage. Mechanistic studies revealed that the effect of RGC-32 on the antiangiogenic response was via attenuating fibroblast growth factor 2 expression and further inhibiting expression of cyclin E without affecting vascular endothelial growth factor and fibroblast growth factor 2 signaling in endothelial cells. In the mouse hind-limb ischemia model, RGC-32 inhibited capillary density with a significant attenuation in blood flow. Additionally, treatment with RGC-32 in the xenograft tumor model resulted in reduced growth of blood vessels that is consistent with reduced colon tumor size.CONCLUSIONS: We provide the first direct evidence for RGC-32 as a hypoxia-inducible gene and antiangiogenic factor in endothelial cells. These data suggest that RGC-32 plays an important homeostatic role in that it contributes to differentiating the pathways for vascular endothelial growth factor and fibroblast growth factor 2 in angiogenesis and provides a new target for ischemic disorder and tumor therapies.
|
|
| 2. |
- Björk, Petra, et al.
(författare)
-
Specific combinations of SR proteins associate with single pre-messenger RNAs in vivo and contribute different functions
- 2009
-
Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 184:4, s. 555-568
-
Tidskriftsartikel (refereegranskat)abstract
- Serine/arginine-rich (SR) proteins are required for messenger RNA (mRNA) processing, export, surveillance, and translation. We show that in Chironomus tentans, nascent transcripts associate with multiple types of SR proteins in specific combinations. Alternative splicing factor (ASF)/SF2, SC35, 9G8, and hrp45/SRp55 are all present in Balbiani ring (BR) pre-messenger ribonucleoproteins (mRNPs) preferentially when introns appear in the pre-mRNA and when cotranscriptional splicing takes place. However, hrp45/SRp55 is distributed differently in the pre-mRNPs along the gene compared with ASF/SF2, SC35, and 9G8, suggesting functional differences. All four SR proteins are associated with the BR mRNPs during export to the cytoplasm. Interference with SC35 indicates that SC35 is important for the coordination of splicing, transcription, and 3' end processing and also for nucleocytoplasmic export. ASF/SF2 is associated with polyribosomes, whereas SC35, 9G8, and hrp45/SRp55 cosediment with mono-ribosomes. Thus, individual endogenous pre-mRNPs/mRNPs bind multiple types of SR proteins during transcription, and these SR proteins accompany the mRNA and play different roles during the gene expression pathway in vivo.
|
|
| 3. |
- Jin, Yi, et al.
(författare)
-
RGS5, a hypoxia-inducible apoptotic stimulator in endothelial cells.
- 2009
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 284:35, s. 23436-43
-
Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells rapidly respond to changes in oxygen homeostasis by regulating gene expression. Regulator of G protein signaling 5 (RGS5) is a negative regulator of G protein-mediated signaling that is strongly expressed in vessels during angiogenesis; however, the role of RGS5 in hypoxia has not been fully understood. Under hypoxic conditions, we found that the expression of RGS5, but not other RGS, was induced in human umbilical vein endothelial cells (HUVEC). RGS5 mRNA was increased when HUVEC were incubated with chemicals that stabilized hypoxia-inducible factor-1alpha (HIF-1alpha), whereas hypoxia-stimulated RGS5 promoter activity was absent in HIF-1beta(-/-) cells. Vascular endothelial growth factor (VEGF), which is regulated by HIF-1, did not appear to be involved in hypoxia-induced RGS5 expression; however, VEGF-mediated activation of p38 but not ERK1/2 was increased by RGS5. Overexpression of RGS5 in HUVEC exhibited a reduced growth rate without affecting the cell proliferation. Annexin V assay revealed that RGS5 induced apoptosis with significantly increased activation of caspase-3 and the Bax/Bcl-2 ratio. Small interfering RNA-specific for RGS5, caspase-3 inhibitor, and p38 inhibitor resulted in an attenuation of RGS5-stimulated apoptosis. Matrigel assay proved that RGS5 significantly impaired the angiogenic effect of VEGF and stimulated apoptosis in vivo. We concluded that RGS5 is a novel HIF-1-dependent, hypoxia-induced gene that is involved in the induction of endothelial apoptosis. Moreover, RGS5 antagonizes the angiogenic effect of VEGF by increasing the activation of p38 signaling, suggesting that RGS5 could be an important target for apoptotic therapy.
|
|
| 4. |
- Lei, Li-Jian, et al.
(författare)
-
Estimation of benchmark dose for pancreatic damage in cadmium-exposed smelters
- 2007
-
Ingår i: Toxicological Sciences. - Oxford : Oxford University Press. - 1096-6080 .- 1096-0929. ; 97:1, s. 189-195
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to estimate the benchmark dose (BMD) for pancreas dysfunction caused by cadmium (Cd) exposure in smelters. Smelter workers who had been exposed to Cd for more than 1 year and matching nonoccupationally exposed subjects were asked to participate in this study. Urinary cadmium (UCd) was used as a biomarker for exposure, serum insulin and amylase were used as biomarkers for pancreatic effects. In this study, serum insulin and amylase were lower in the smelter workers than in the nonoccupationally exposed subjects. A significant dose-response relationship with UCd was displayed. BMI)s in terms of urinary Cd corrected for creatinine were calculated by use of BMDS (version 1.3.2). The benchmark dose lower limit of a one-sided 95% confidence interval (BMDL) for 10% excess risk was also determined. It was found that the BMDL10 for serum insulin and serum amylase was 3.7 and 5.3 mu g/g Cr, respectively. Compared to the BMDL for renal damage caused by Cd exposure, identified by the effect biomarkers urinary beta(2)-microglobulin, urinary N-acetyl-beta-glucosaminidase, and urinary albumin (UALB), it was shown that BMDL10 for serum insulin is the lowest among all values and UALB gave the highest value (5.8 mu g/g Cr). This study indicates that Cd exposure can result in pancreatic dysfunction and the effect appears at lower urinary Cd level than renal dysfunction. The endocrine function of the pancreas was affected at lower urinary levels of Cd, compared to the exocrine function, which was seen at higher urinary levels of Cd than those giving rise to renal tubular dysfunction.
|
|
| 5. |
- Lu, Jian, et al.
(författare)
-
Metallothionein gene expression in peripheral lymphocytes and renal dysfunction in a population environmentally exposed to cadmium.
- 2005
-
Ingår i: Toxicology and applied pharmacology. - : Elsevier BV. - 0041-008X. ; 206:2, s. 150-6
-
Tidskriftsartikel (refereegranskat)abstract
- In order to study the validity of metallothionein (MT) gene expression in peripheral blood lymphocytes (PBLs) as a biomarker of cadmium exposure and susceptibility to renal dysfunction, MT mRNA levels were measured using reverse transcription polymerase chain reaction (RT-PCR) in PBLs from residents living in a cadmium-contaminated area. MT mRNA levels were found to increase with the increase of blood cadmium (BCd) and urinary cadmium (UCd) levels. Basal MT mRNA levels were significantly correlated with the logarithm of BCd levels and the logarithm of UCd levels confirming that MT expression in PBLs is a biomarker of cadmium exposure and internal dose. An inverse relationship was observed between in vitro induced MT-mRNA level in PBLs and urinary N-acetyl-beta-d-glucosaminidase (UNAG) suggesting that MT gene expression in PBLs may be used as a biomarker of susceptibility to renal toxicity of cadmium.
|
|
| 6. |
- Lu, Yuan-Yuan, et al.
(författare)
-
A clinical study of microcirculatory disturbance in Chinese patients with sudden deafness
- 2008
-
Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 128:11
-
Tidskriftsartikel (refereegranskat)abstract
- Conclusion. Cochlear microcirculation disturbance is closely associated with sudden deafness. Objectives. To investigate the relationship between cochlear microcirculation and sudden deafness. Subjects and methods. Clinical laboratory parameters (clinical chemistry, hemorheology, hematology, and hemostasis determinations) were studied in 86 patients with sudden deafness and 30 healthy control subjects. Results. The levels of total cholesterol (TCH), triglyceride (TG), and lipoprotein A were significantly higher in patients with sudden deafness than in control subjects. Plasma viscosity, ratio viscosity of whole blood, reduced viscosity of whole blood, high and low shear relative viscosity of whole blood, index of red blood cells transmutation, and fibrinogen level in the plasma of patients with sudden sensorineural hearing loss (SSNHL) were also significantly elevated in comparison with those in control subjects. White-collar workers with psychological and behavioral abnormalities tend to suffer from sudden deafness.
|
|
| 7. |
- Nordberg, Gunnar F, et al.
(författare)
-
Prevalence of kidney dysfunction in humans - relationship to cadmium dose, metallothionein, immunological and metabolic factors.
- 2009
-
Ingår i: Biochimie. - : Elsevier BV. - 1638-6183 .- 0300-9084. ; 91:10, s. 1282-5
-
Tidskriftsartikel (refereegranskat)abstract
- Long term cadmium (Cd) exposure in occupational and general environments may give rise to kidney dysfunction. This effect is usually considered to be the critical effect, i. e. the effect that occurs at relatively low level of exposure. The present review focused on studies of the prevalence of cadmium-related kidney dysfunction among population groups residing in cadmium contaminated areas in China. Dose-response relationships were shown between UCd and the prevalence of increased levels of biomarkers in urine of renal tubular dysfunction such as urinary beta-2-microglobulin or N-acetyl-beta-d-glucosaminidase - NAG or urinary albumin, a biomarker of glomerular kidney dysfunction. Factors that influence these dose-response relationships include: 1) Metallothionein mRNA levels in peripheral blood lymphocytes, used as a biomarker of the ability of each person, to synthesize metallothionein (a protein known to provide intracellular protection against cadmium toxicity). 2) The occurrence of increased levels in blood plasma of autoantibodies against metallothionein. 3) Concomitant changes in glucose metabolism i e Type II diabetes. 4) Concomitant exposure to other nephrotoxic agents such as inorganic arsenic. Increased susceptibility in diabetics has been shown also in population groups in Europe. In persons with type II diabetes and increased levels of autoantibodies against metallothionein in blood plasma or in persons with concomitant exposure to environmental inorganic arsenic, indications of Cd-related kidney dysfunction was observed at UCd levels around 1 microg/g creatinine, levels found among "unexposed" population groups in many countries.
|
|
| 8. |
|
|
| 9. |
- Su, Zhi-Jian, et al.
(författare)
-
Criterion for Dendrite Fragmentation of Carbon Steel under Imposition of Linear Travelling EMS
- 2009
-
Ingår i: STEEL RESEARCH INTERNATIONAL. - 1611-3683. ; 80:11, s. 824-833
-
Tidskriftsartikel (refereegranskat)abstract
- In this study the columnar-to-equiaxed transition (CET) of carbon steel with 0.22-0.98 mass%C is investigated, based on the dendrite fragmentation theory of T. Campanella et al. The following conclusions are obtained: The criterion for dendrite fragmentation under linear EMS is obtained and verified by the 0.22-0.98 mass%C steel experiments. Investigation is carried out on the relation between the superficial velocity of the liquid phase and the actual velocity of the interdendritic liquid and the volume fraction of solid at the time of dendrite fragmentation (CET occurrence). At the same superficial velocity, the dendrite fragmentation critical volume fraction of solid is smaller in the case of high carbon steel. As a result, the CET occurrence is more difficult in the case of high carbon steel. Dendrite fragmentation induced by EMS is confirmed by the fragments of dendrite arms observed in the macrostructure. The length of dendrite fragmentation observed is about 1mm
|
|
