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Suppression of Par-4 protects human renal proximal tubule cells from apoptosis induced by oxidative stress.
MedLine Citation:
PMID:  20814219     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND: Oxidative stress is an important inducer of cell apoptosis and plays a key role in the development of renal inflammation. The prostate apoptosis response factor-4 (Par-4) gene was originally identified in prostate cells undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro-apoptotic activity in various cellular systems. However, it remains unclear whether Par-4 is involved in oxidant injury of renal tubular epithelial cells.
AIMS: To determine the role of Par-4 in renal proximal tubular cell apoptosis induced by oxidative stress.
METHODS: Par-4 gene expression was silenced by small interfering RNA. Renal proximal tubular cells were then exposed to hydrogen peroxide and the effect of Par-4 silencing on apoptosis and expression of phosphorylated Akt and vascular endothelial growth factor was determined.
RESULTS: Hydrogen peroxide induced apoptosis and increased Par-4 expression in human renal proximal tubular epithelial cells. Par-4 silencing significantly protected renal proximal tubular cells from apoptosis via activating the PI3K/Akt signaling pathway as Akt phosphorylation was enhanced. Par-4 silencing also ameliorated the downregulation of vascular endothelial growth factor expression induced by oxidative stress.
CONCLUSION: Par-4 gene silencing resulted in PI3K/Akt signaling-dependent inhibition of renal proximal tubular cell apoptosis following oxidative stress.
Authors:
Bin Sun; Chao Lu; Guo-Ping Zhou; Chang-Ying Xing
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nephron. Experimental nephrology     Volume:  117     ISSN:  1660-2129     ISO Abbreviation:  Nephron Exp. Nephrol.     Publication Date:  2011  
Date Detail:
Created Date:  2011-04-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101159770     Medline TA:  Nephron Exp Nephrol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  e53-61     Citation Subset:  IM    
Affiliation:
Division of Nephrology, Department of Internal Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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