| 1. |
- Chaillou, Thomas, 1985-, et al.
(författare)
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Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration
- 2014
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Ingår i: Molecular and Cellular Biochemistry. - : Kluwer Academic Publishers. - 0300-8177 .- 1573-4919. ; 390:1-2, s. 31-40
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia impairs the muscle fibre-type shift from fast-to-slow during post-natal development; however, this adaptation could be a consequence of the reduced voluntary physical activity associated with hypoxia exposure rather than the result of hypoxia per se. Moreover, muscle oxidative capacity could be reduced in hypoxia, particularly when hypoxia is combined with additional stress. Here, we used a model of muscle regeneration to mimic the fast-to-slow fibre-type conversion observed during post-natal development. We hypothesised that hypoxia would impair the recovery of the myosin heavy chain (MHC) profile and oxidative capacity during muscle regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14 and 28 days under normoxia or hypobaric hypoxia (5,500 m altitude) conditions. Ambient hypoxia did not impair the recovery of the slow MHC profile during muscle regeneration. However, hypoxia moderately decreased the oxidative capacity (assessed from the activity of citrate synthase) of intact muscle and delayed its recovery in regenerated muscle. Hypoxia transiently increased in both regenerated and intact muscles the content of phosphorylated AMPK and Pgc-1α mRNA, two regulators involved in mitochondrial biogenesis, while it transiently increased in intact muscle the mRNA level of the mitophagic factor BNIP3. In conclusion, hypoxia does not act to impair the fast-to-slow MHC isoform transition during regeneration. Hypoxia alters the oxidative capacity of intact muscle and delays its recovery in regenerated muscle; however, this adaptation to hypoxia was independent of the studied regulators of mitochondrial turn-over.
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| 2. |
- Holm, Anders, et al.
(författare)
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The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner.
- 2012
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Ingår i: Molecular and Cellular Biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 366:1-2, s. 239-249
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Tidskriftsartikel (refereegranskat)abstract
- The G protein-coupled oestrogen receptor GPER1, also known as GPR30, has been implicated in oestrogen signalling, but the physiological importance of GPER1 is not fully understood. The GPER1 agonist G-1 has become an important tool to assess GPER1-mediated cellular effects. Here, we report that this substance, besides acting via GPER1, affects the microtubule network in endothelial cells. Treatment with G-1 (3 μM) for 24 h reduced DNA synthesis by about 60 % in mouse microvascular endothelial bEnd.3 cells. Treatment with 3 μM G-1 prevented outgrowth of primary endothelial cells from mouse aortic explants embedded in Matrigel. Treatment with G-1 (0.3-3 μM) for 24 h disrupted bEnd.3 cell and HUVEC microtubule structure in a concentration-dependent manner as assessed by laser-scanning confocal immunofluorescence microscopy. G-1-induced (3 μM) disruption of microtubule was observed also after acute (3 and 6 h) treatment and in the presence of the protein synthesis inhibitor cycloheximide. Disruption of microtubules by 3 μM G-1 was observed in aortic smooth muscle cells obtained from both GPER1 knockout and wild-type mice, suggesting that G-1 influences microtubules through a mechanism independent of GPER1. G-1 dose dependently (10-50 μM) stimulated microtubule assembly in vitro. On the other hand, microtubules appeared normal in the presence of 10-50 μM G-1 as determined by electron microscopy. We suggest that G-1-promoted endothelial cell anti-proliferation is due in part to alteration of microtubule organization through a mechanism independent of GPER1. This G-1-promoted mechanism may be used to block unwanted endothelial cell proliferation and angiogenesis such as that observed in, e.g. cancer.
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| 3. |
- Krivoruchko, Anastasia, 1984, et al.
(författare)
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Activation of the unfolded protein response during anoxia exposure in the turtle Trachemys scripta elegans
- 2013
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Ingår i: Molecular and Cellular Biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 374:1-2, s. 91-103
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Tidskriftsartikel (refereegranskat)abstract
- Red-eared slider turtles, Trachemys scripta elegans, can survive for several weeks without oxygen when submerged in cold water. We hypothesized that anaerobiosis is aided by adaptive up-regulation of the unfolded protein response (UPR), a stress-responsive pathway that is activated by accumulation of unfolded proteins in the endoplasmic reticulum (ER) and functions to restore ER homeostasis. RT-PCR, western immunoblotting and DNA-binding assays were used to quantify the responses and/or activation status of UPR-responsive genes and proteins in turtle tissues after animal exposure to 5 or 20 h of anoxic submergence at 4 C. The phosphorylation state of protein kinase-like ER kinase (PERK) (a UPR-regulated kinase) and eukaryotic initiation factor 2 (eIF2α) increased by 1.43-2.50 fold in response to anoxia in turtle heart, kidney, and liver. Activation of the PERK-regulated transcription factor, activating transcription factor 4 (ATF4), during anoxia was documented by elevated atf4 transcripts and total ATF4 protein (1.60-2.43 fold), increased nuclear ATF4 content, and increased DNA-binding activity (1.44-2.32 fold). ATF3 and GADD34 (downstream targets of ATF4) also increased by 1.38-3.32 fold in heart and liver under anoxia, and atf3 transcripts were also elevated in heart. Two characteristic chaperones of the UPR, GRP78, and GRP94, also responded positively to anoxia with strong increases in both the transcript and protein levels. The data demonstrate that the UPR is activated in turtle heart, kidney, and liver in response to anoxia, suggesting that this pathway mediates an integrated stress response to protect tissues during oxygen deprivation. © 2012 Springer Science+Business Media New York.
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| 4. |
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| 5. |
- Shah, Viral N., et al.
(författare)
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ACAC beta gene (rs2268388) and AGTR1 gene (rs5186) polymorphism and the risk of nephropathy in Asian Indian patients with type 2 diabetes
- 2013
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Ingår i: Molecular and Cellular Biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 372:1-2, s. 191-198
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Tidskriftsartikel (refereegranskat)abstract
- Patients with type 2 diabetes (T2DM) are usually obese and concurrent obesity results into activation of the renin-angiotensin-system (RAS) which is a risk factor for diabetic nephropathy (DN). Gene-gene interaction between acetyl-coenzymeA carboxylase beta (ACAC beta) gene, which is involved in fatty acid metabolism and angiotensin II receptors (AGTR1) gene, which mediates RAS proteins actions on renal tissue, polymorphism with DN have not been studied earlier. The present study was designed with the aim to examine the association of an ACAC beta (rs2268388) and AGTR1 (rs5186) gene polymorphism with the risk of DN in Asian Indians. 1,158 patients with T2DM belonging to two independently ascertained North Indian and one South Indian cohorts were genotyped for ACAC beta (rs2268388) and AGTR1 (rs5186) polymorphism using real time PCR-based Taq-man assay and PCR-RFLP assays. In all the three cohorts, a significantly higher frequency of T allele and TT genotypes of ACAC beta and C allele and CC genotypes of AGTR1 were found in patients with DN as compared to patients without nephropathy. Further, T allele of ACAC beta and C allele of AGTR1 were found to be significantly associated with proteinuria, a hallmark of DN. We also found significant epistatic interactions between these two genes. TT genotypes of ACAC beta gene and CC genotype of AGTR1 gene confers the risk of DN and both genes had significant epistatic interaction in Asian Indian patients with T2DM.
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| 6. |
- Shao, Yangzhen, 1981, et al.
(författare)
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Lipid metabolites and their differential pro-arrhythmic profiles: of importance in the development of a new anti-arrhythmic pharmacology.
- 2014
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Ingår i: Molecular and cellular biochemistry. - : Springer Science and Business Media LLC. - 1573-4919 .- 0300-8177. ; 393:1-2, s. 191-197
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Tidskriftsartikel (refereegranskat)abstract
- Arrhythmias have been treated for a long time with drugs that mainly target the ionic pumps and channels. These anti-arrhythmic regimens per se introduce new arrhythmias, which can be detrimental to patients. Advances in development of novel pharmacology without introduction of iatrogenic arrhythmias are thus favorable for an effective treatment of arrhythmias. Electrophysiological stability of the heart has been shown to be closely associated with cardiac metabolism. The present effective anti-arrhythmic drugs such as beta-blockers and amiodarone have profound beneficial effects in regulating myocardial metabolism. Aiming at decreasing production of toxic metabolites or preventing accumulation of arrhythmogenic lipids perhaps is a good strategy to effectively control arrhythmias. Therefore, a better understanding of the pro-arrhythmic profiles of cardiac metabolites helps to explore a new generation of metabolically oriented anti-arrhythmic medications. In this review, we present several lipid metabolites and summarize their arrhythmogenic characteristics.
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| 7. |
- Sobti, Ranbir Chander, et al.
(författare)
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Genetic variants of EGFR (142285G>A) and ESR1 (2014G>A) gene polymorphisms and risk of breast cancer
- 2012
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Ingår i: Molecular and Cellular Biochemistry. - : Springer Science+Business Media B.V.. - 0300-8177 .- 1573-4919. ; 369:1-2, s. 217-25
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is one of the most common cancers in women worldwide. The estrogen receptor alpha (ESR1) and epidermal growth factor receptor (EGFR) have been known to play a vital role in development and progression of breast cancer. The aim of the present study was to determine the relationship, if any, between genetic polymorphism in (ESR1) 2014G>A (T594T) and (EGFR) 142285G>A (R521K) with risk of breast cancer and the prognosis in a heterogeneous North Indian population that is known for its diverse ethnicity. A case-control study in a total of 300 individuals comprising of 150 breast cancer patients and 150 normal controls was performed. PCR-RFLP was employed for genotyping. The G/A heterozygous genotype EGFR R521K, was slightly higher in cases (56.7 %) than in controls (48.3 %) (P = 0.20). The results indicated that EGFR polymorphism does not show any significant association with breast cancer in this population. On the other hand, the mutant A/A genotype ESR1 codon 594, showed a 6.4-folds risk for breast cancer and this association was highly significant (P = 0.00) as compared to wild GG genotype, the heterozygous G/A genotype also showed a significant association with disease (P = 0.00, OR = 2.03). In addition, the frequency of A allele was also higher in cases (36 %) than in controls (19 %) and a highly significant difference was observed with wild G allele (63.3 % in cases and 6.6 % in controls). This clearly indicates that there appears to be an influence of ESR1 codon 594 genotypes on genetic susceptibility to breast cancer. Further a significantly higher risk was observed in individuals who had diabetes {OR = 3.04 (1.68-5.50), P = 0.00} and females with ESR polymorphism in pre-menopause patients that had undergone menopause above the age of 50 years {OR = 3.58 (1.86-6.90), P < 0.05}. The different ethnic backgrounds and geographical locations have complimented the present genotypic analysis and have highlighted the influence of ethnicity, race and geographic location in genetic predisposition to breast cancer.
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| 8. |
- Sobti, Ranbir Chander, et al.
(författare)
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Impact of XPD gene polymorphism on risk of prostate cancer on north Indian population
- 2012
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Ingår i: Molecular and Cellular Biochemistry. - : Springer Science+Business Media B.V.. - 0300-8177 .- 1573-4919. ; 362:1-2, s. 263-8
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is the second most diagnosed cancer in men next to skin cancer in the developed world. Risk of disease varies most prominently with age, ethnicity, family history, and diet. Genetic polymorphism of some genes has been implicated in increasing the risk. The XPD (Xeroderma pigmentosum group D) gene codes for a DNA helicase involved in transcription and nucleotide excision repair. The aim of this study is to evaluate the effect of XPD 751 Lys/Gln polymorphism on risk of prostate cancer on north Indian patients. Blood sample from 150 prostate cancer patients, 150 from Prostate Hyper Plasia and equal number of samples from healthy control groups was collected from North India. The polymerase chain reaction and restrictive fragment length polymorphism techniques were implemented. Statistically non-significant increase risk of prostate cancer was observed with patients having Gln/Gln genotype (OR 1.62, 95% CI).
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| 9. |
- Sobti, Ranbir Chander, et al.
(författare)
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Risk of obesity and type 2 diabetes with tumor necrosis factor-α 308G/A gene polymorphism in metabolic syndrome and coronary artery disease subjects
- 2012
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Ingår i: Molecular and Cellular Biochemistry. - : Springer. - 0300-8177 .- 1573-4919. ; 360:1-2, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Tumor Necrosis Factor-alpha (TNF-α) has been implicated in the pathogenesis of insulin resistance and obesity. The increased expression of TNF-α in adipose tissue is known to induce insulin resistance, and a polymorphism at position -308 in the promoter region of TNF-α gene may lead to its increased transcription in adipocytes. The objective of this work was to determine the role of TNFα-308G/A gene polymorphism in metabolic syndrome (MetS) and coronary artery disease (CAD) with obesity and type 2 diabetes mellitus (T2DM). A total of 250 MetS and 224 CAD patients and 214 controls were studied. TNFα-308G/A polymorphism was detected from the whole blood genomic DNA using PCR-amplification refractory mutation system. The 2 × 2 contingency tables and multiple regression analysis were used for determining the association of genotypes with obesity and type 2 diabetes mellitus (T2DM) in MetS and CAD subjects. In CAD subjects with T2DM, the AG genotypes showed a very strong association (P < 0.0001; OR 0.194, 95%CI 0.103-0.365). In CAD subjects with obesity, the AA (P = 0.049; OR 2.449) and AG genotypes showed a strong association (P < 0.0001; OR 0.206). In both males and females, AG genotype and G allele (P < 0.0001) showed a strong association with T2DM. In MetS subjects with T2DM, there was a strong association with AG (P = 0.002; OR 4.483) as well as AA+AG genotypes (P = 0.002; OR 4.255). The AA and AG genotype (P = 0.001; OR 5.497) in males showed a strong 4.6- and 5.4-fold risks, respectively, with obesity. In females, only AG genotype showed a strong 4.5-fold risk with obesity (P = 0.001). In MetS subjects with obesity, the AA genotype (P = 0.043; OR 3.352) as well as AG showed a very strong association (P = 0.001; OR 5.011). The AG genotypes showed a high 3.5-fold risk with T2DM in females (P = 0.011). In CAD subjects, AG genotype showed a protective effect in both obese males and females (P < 0.0001). Heterozygous TNFα-308G/A gene variant may be an important risk factor for MetS with T2DM and obesity in both males and females, but may have a protective role in CAD subjects with obesity and T2DM. A allele may be an important risk factor for MetS and CAD with obesity as well as CAD subjects with T2DM.
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| 10. |
- Wallerstedt, Emelie, 1981, et al.
(författare)
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Anti-inflammatory effect of insulin in the human hepatoma cell line HepG2 involves decreased transcription of IL-6 target genes and nuclear exclusion of FOXO1
- 2011
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Ingår i: Molecular and Cellular Biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 352:1-2, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- The liver is an important target for interleukin-6 (IL-6) action leading to an increased inflammatory response with impaired insulin signaling and action. The aims of this study are to address if insulin is anti-inflammatory and attenuates IL-6-induced inflammation in the human hepatoma cell line HepG2 and if this involves signal transducer and activator of transcription 3 (STAT3) signal transduction. It was found that insulin significantly reduced IL-6-induced gene transcription of serum amyloid 1 (SAA1), serum amyloid 2 (SAA2), haptoglobin, orosomucoid, and plasmin activator inhibitor-1 (PAI-1). However, the authors did not find any evidence that insulin inhibited IL-6 signal transduction, i.e., no effect of insulin was detected on STAT3 phosphorylation or its translocation to cell nucleus. The potential role of PKCdelta was also analyzed but no evidence of its involvement was found. Taken together, these results suggest that the anti-inflammatory effect of insulin on IL-6 action is exerted at the level of the transcriptional activation of the genes. Further analysis revealed that insulin regulates nuclear localization of FOXO1, which is an important co-activator for STAT3 mediated transcription. Insulin induced nuclear exit and Thr24 phosphorylation of FOXO1, thus, inhibiting STAT3-mediated transcription.
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