Cellular Stress and Ageing Program

Düsseldorf, Germany

Cellular Stress and Ageing Program

Düsseldorf, Germany

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Zhou T.-B.,Sun Yat Sen University | Zhao H.-L.,Guangxi Medical University | Fang S.-L.,Sun Yat Sen University | Drummen G.P.C.,Cellular Stress and Ageing Program
Journal of Receptors and Signal Transduction | Year: 2014

The association of transforming growth factor-β1 (TGFβ1) is an important signaling pathway factor involving extracellular matrix regulation, and its gene polymorphisms with the risk of rheumatoid arthritis (RA) is currently still fiercely debated. Therefore, this meta-analysis was performed to determine if TGFβ1 T869C, G915C, and C509T gene polymorphisms correlate with the risk of developing RA. Association reports were identified from PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) on 1 May 2013, and eligible studies were recruited and synthesized to identifying patterns among study results. T869C TT genotype in the overall population was associated with increased RA risk (OR=1.28, 95% CI: 1.02-1.60, p=0.03). In the sub-group analysis, T869C TT genotype was shown to be a risk factor for RA, and T869C C allele or CC genotype a protective factor against RA disease in Asians, but these associations were not found in Caucasians. Furthermore, TGFβ1 C509T TT genotype was distinctly associated with RA susceptibility, but the T allele and CC genotype were not. TGFβ1 G915C gene polymorphism was not associated with RA susceptibility. In conclusion, the TT genotype of TGFβ1 T869C was associated with RA risk in the overall population and Asians. Furthermore, CC genotype or C allele was determined to be protective factors with respect to the RA risk in the overall population and Asians. Nonetheless, additional studies are required to firmly establish a correlation between the aforementioned polymorphisms and RA risk. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.


Zhou T.-B.,Sun Yat Sen University | Zhou T.-B.,Guangxi Medical University | Qin Y.-H.,Guangxi Medical University | Lei F.-Y.,Guangxi Medical University | And 2 more authors.
Molecular Biology Reports | Year: 2014

Prohibitins PHB1 and PHB2 are evolutionary conserved and pleiotropic proteins, which have been shown to be important factors in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. Recently, we demonstrated that down-regulation promoted renal interstitial fibrosis (RIF) in ureteral obstructed rats. Furthermore, the hypoxic conditions and oxidative stress have been implicated in obstruction-mediated renal disease. This study was performed to explore the association of PHBs with oxidative stress in a rat model of RIF. PHBs, the profibrotic transforming growth factor-β1 (TGF-β1), and the extracellular matrix proteins collagen-IV (Col-IV) and fibronectin (FN) were evaluated, as were markers of oxidative stress [total reactive oxygen species (ROS), malondialdehyde (MDA)] and antioxidative capacity (superoxide dismutase, glutathione), and apoptosis. Our results showed a progressive increase in oxidative stress and concomitant decrease in antioxidants over a period of 4 weeks ureteral obstruction. Concomitantly, profibrotic components increased and PHB expression decreased. Overall, both PHBs were negatively correlated with the extent of observed fibrosis, TGF-β1, Col-IV, FN, ROS, MDA, and apoptosis. © Springer Science+Business Media 2014.


Zhou T.-B.,Sun Yat Sen University | Ou C.,Guangxi Medical University | Rong L.,Baylor College of Medicine | Drummen G.P.C.,Cellular Stress and Ageing Program
JRAAS - Journal of the Renin-Angiotensin-Aldosterone System | Year: 2014

Background and objective: All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensin- aldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis.Methods: The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/ reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment.Results: Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA (PHB1: r = -0.792, -0.834, -0.805, -0.795, -0.778, -0.798, -0.751, -0.682; PHB2: r = -0.872, -0.799, -0.838, -0.773, -0.769, -0.841, -0.794, -0.826; each p<0.05), but positively correlated with ACE2, SOD, and GSH (PHB1: r = 0.796, 0.879, 0.824; PHB2: r = 0.785, 0.914, 0.849; each p<0.05). ACE1 was positively correlated with angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and negatively correlated with ACE2, SOD, and GSH (each p<0.05). ACE2 was negatively correlated with ACE1, angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and positively correlated with SOD and GSH (each p<0.05).Conclusion: The results suggest that ATRA acts as a positive regulator of PHB1, PHB2 and ACE2, and as a negative regulator of ACE1, angiotensin I, and angiotensin II in a RTEC model system under hypoxia/reoxygenation conditions. © The Author(s) 2012.


Zhou T.-B.,Sun Yat Sen University | Drummen G.P.C.,Cellular Stress and Ageing Program | Jiang Z.-P.,Sun Yat Sen University | Li H.-Y.,Southern Medical University
Renal Failure | Year: 2015

Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme that regulates nucleotide synthesis and DNA methylation. The MTHFR C677T gene polymorphism (rs1801133), a C → T transition at nucleotide 677 in exon 4, is a common gene variant of MTHFR and has been implicated in diabetic nephropathy, albeit with inconsistent results. Here, we performed a meta-analysis to assess the common effect size of this polymorphism on DN susceptibility. Case-control studies on the association of the MTHFR C677T gene polymorphism with DN risk were retrieved from databases up to August 1, 2013, and eligible studies were recruited into the meta-analysis and further analyzed. Of 132 studies, 33 were identified as suitable for this analysis. The results showed that T allele and TT genotype were distinctly associated with DN susceptibility in the overall population and Asians, and might be a risk factor in Caucasians and Africans (T allele: Overall population: p < 0.00001, Asians: p = 0.0002, Caucasians: p = 0.02, Africans: p < 0.00001; TT genotype: Overall population: p < 0.00001, Asians: p = 0.0003, Caucasians: p = 0.008, Africans: p = 0.0003). Furthermore, the analysis suggested that the CC genotype might play a protective role against DN onset in patients with type 2 diabetes for the overall population, Asians, Caucasian and Africans. However, due to the limited sample size in the African population, these results should be interpreted with care. In conclusion, the MTHFR C677T T allele or TT genotype might be a significant genetic molecular marker to determine the risk of DN in patients with type 2 diabetes and help to develop suitable disease prevention and management strategies. © 2015 Informa Healthcare USA, Inc.


Zhou T.-B.,Sun Yat Sen University | Jiang Z.-P.,Sun Yat Sen University | Qin Y.-H.,Guangxi Medical University | Drummen G.P.C.,Cellular Stress and Ageing Program
Nephrology | Year: 2014

Aim A possible association between the transforming growth factor-β1 (TGF-β1) T869C gene polymorphism and the risk of developing diabetic nephropathy (DN) remains unclear. This investigation was performed to assess if an association between the TGF-β1 T869C gene polymorphism and DN risk exists by using meta-analysis to combine comparable studies, thereby increasing sample size and statistical significance, and to identify patterns in various studies. Methods The association reports were identified from PubMed, Cochrane Library, and CBM-disc (China Biological Medicine Database) on 1 May 2013, and eligible studies were recruited and synthesized. Results Fifty reports were recruited into this meta-analysis for the association of the TGF-β1 T869C gene polymorphism with DN risk. The TT genotype in the overall population was shown to be associated with DN risk (odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.56-0.98, P = 0.04). In the sub-group analysis, CC genotype was associated with DN risk in Asians, Caucasians, and Africans. However, the sample size for Caucasians and Africans was relatively small. Furthermore, T allele was distinctly associated with the risk of developing DN in the Asian population (OR = 0.76, 95% CI: 0.62-0.92, P = 0.005). Conclusions The TT genotype of TGF-β1 T869C in the overall population was associated with DN risk, whereas the CC genotype and T allele were distinctly associated with DN risk in the Asian population. Nonetheless, additional studies are required to firmly establish a correlation between the aforementioned polymorphism and DN risk. Summary at a Glance Previous studies have investigated a potential link between gene polymorphism of TGF-β1 and the risk of diabetic kidney disease but the data are not conclusive. In this study, the authors have used a meta-analytic approach to provide further data on the role of the TGF-β1 T869C gene polymorphism as a predictor of diabetic nephropathy. © 2013 Asian Pacific Society of Nephrology.


Zhou T.-B.,Guangxi Medical University | Zhou T.-B.,Sun Yat Sen University | Qin Y.-H.,Guangxi Medical University | Lei F.-Y.,Guangxi Medical University | And 2 more authors.
PLoS ONE | Year: 2013

Prohibitin is an evolutionary conserved and pleiotropic protein that has been implicated in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. Both prohibitin over- and under-expression have been implicated in various diseases and cell types. We recently demonstrated that prohibitin down-regulation results in increased renal interstitial fibrosis (RIF). Here we investigated the role of oxidative stress and prohibitin expression in RIF in unilateral ureteral obstructed rats. Lentivirus-based delivery vectors were used to knockdown or over-express prohibitin. Our results show that increased prohibitin expression was negatively correlated with the RIF index, reactive oxygen species, malon dialdehyde, transforming growth factor β1, collagen IV, fibronectin, and cell apoptosis index. In conclusion, we postulate that prohibitin acts as a positive regulator of mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect. © 2013 Zhou et al.


Zhou T.-B.,Sun Yat Sen University | Zhou T.-B.,Guangxi Medical University | Drummen G.P.C.,Cellular Stress and Ageing Program | Jiang Z.-P.,Sun Yat Sen University | And 2 more authors.
Journal of Receptors and Signal Transduction | Year: 2013

Peroxisome proliferator-activated receptor-γ (PPARγ), belongs to the nuclear receptor superfamily, and is a nuclear transcription receptor involving in the regulation of several biochemical pathways, such as cell growth, differentiation, and apoptosis. The nuclear retinoic acid receptors (RARs) are transcriptional transregulators that control the expression of specific subsets of genes in a ligand-dependent manner, and include three subtypes (RARα, RARβ, and RARγ). These control the expression of specific gene subsets subsequent to ligand binding and to strictly control phosphorylation processes. The current status of knowledge indicates that there might be inter- or overlapping actions between PPARγ and RARs, and there might be an association of PPARγ/RARs with renal diseases. Various agonists of both receptor families seem to prevent or retard the progression of renal disease. Herein, we review if causal relationships can be established between PPARγ/RARs and renal diseases and its manifestations. © 2013 Informa Healthcare USA, Inc.


Zhou T.-B.,Guangxi Medical University | Zhou T.-B.,Sun Yat Sen University | Qin Y.-H.,Guangxi Medical University | Lei F.-Y.,Guangxi Medical University | And 2 more authors.
Scientific Reports | Year: 2013

Prohibitin is an evolutionary conserved and pleiotropic protein that has been implicated in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. We recently demonstrated that prohibitin downregulation results in increased renal interstitial fibrosis. Here we investigated the role of oxidative stress and prohibitin expression in a hypoxia/reoxygenation injury system in renal tubular epithelial cells with lentivirus-based delivery vectors to knockdown or overexpress prohibitin. Our results show that increased prohibitin expression was negatively correlated with reactive oxygen species, malon dialdehyde, transforming-growth-factor-β1, collagen-IV, fibronectin, and apoptosis (r = -0.895, -0.764, -0.798, -0.826, -0.817, -0.735; each P < 0.01), but positively correlated with superoxide dismutase, glutathione and mitochondrial membrane potential (r = 0.807, 0.815, 0.739; each P < 0.01). We postulate that prohibitin acts as a positive regulator of mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect.


Zhou T.-B.,Guangxi Medical University | Drummen G.P.C.,Cellular Stress and Ageing Program | Qin Y.-H.,Guangxi Medical University
International Journal of Molecular Sciences | Year: 2013

Fibrotic diseases, such as liver, pulmonary and renal fibrosis, are common end-stage conditions and represent a major global health problem. Furthermore, effective therapeutic measures are presently unavailable. Extracellular matrix accumulation is the most prominent characteristic in the pathogenesis of fibrotic disease. Retinoic acid, including all-trans retinoic acid, 9-cis and 13-cis retinoic acid, play important roles in various physiological processes, such as in embryonic development, reproduction, vision, cell growth, differentiation, apoptosis and inflammation. Present studies report that retinoic acid treatment may affect various processes involved in the onset and progression of fibrotic disease. However, the therapeutic effects of retinoic acid in such diseases remain controversial. Several reports indicate that retinoic acid positively affects the progression of fibrosis and alleviates the accumulation of the extracellular matrix, whereas other studies report the opposite; that retinoic acid exacerbates fibrosis and induces extracellular matrix accumulation. Signaling pathways might be an important influencing factor and differences in signaling events might be responsible for the contradictory role of retinoic acid in fibrotic diseases. Since there was no review available that investigated the role of retinoic acid and the signaling pathways involved, we retrospectively studied the literature and provide a comprehensive analysis of retinoic acid's role in fibrotic diseases, and provide an overview of the signal transduction pathways involved in its pathogenesis. © 2013 by the authors; licensee MDPI, Basel, Switzerland.


Soltani N.,University Putra Malaysia | Saion E.,University Putra Malaysia | Erfani M.,University Putra Malaysia | Rezaee K.,University of Isfahan | And 4 more authors.
International Journal of Molecular Sciences | Year: 2012

Zinc sulfide semiconductor nanoparticles were synthesized in an aqueous solution of polyvinyl pyrrolidone via a simple microwave irradiation method. The effect of the polymer concentration and the type of sulfur source on the particle size and dispersion of the final ZnS nanoparticle product was carefully examined. Microwave heating generally occurs by two main mechanisms: dipolar polarization of water and ionic conduction of precursors. The introduction of the polymer affects the heating rate by restriction of the rotational motion of dipole molecules and immobilization of ions. Consequently, our results show that the presence of the polymer strongly affects the nucleation and growth rates of the ZnS nanoparticles and therefore determines the average particle size and the dispersion. Moreover, we found that PVP adsorbed on the surface of the ZnS nanoparticles by interaction of the C-N and C=O with the nanoparticle's surface, thereby affording protection from agglomeration by steric hindrance. Generally, with increasing PVP concentration, mono-dispersed colloidal solutions were obtained and at the optimal PVP concentration (5%), sufficiently small size and narrow size distributions were obtained from both sodium sulfide and thioacetamide sulfur sources. Finally, the sulfur source directly influences the reaction mechanism and the final particle morphology, as well as the average size. © 2012 by the authors; licensee MDPI, Basel, Switzerland.

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