Document Detail


Activation of peroxisome proliferator-activated receptor-γ coactivator 1α ameliorates mitochondrial dysfunction and protects podocytes from aldosterone-induced injury.
MedLine Citation:
PMID:  22648295     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glomerular podocytes are highly specialized epithelial cells whose injury in glomerular diseases causes proteinuria. Since mitochondrial dysfunction is an early event in podocyte injury, we tested whether a major regulator of oxidative metabolism and mitochondrial function, the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), affects podocyte damage. Aldosterone-induced injury decreased PGC-1α expression, and induced mitochondrial and podocyte damage in dose- and time-dependent manners. The suppression of endogenous PGC-1α by RNAi caused podocyte mitochondrial damage and apoptosis while its increase by infection with an adenoviral vector prevented aldosterone-induced mitochondrial malfunction and inhibited injury. Overexpression of the silent mating type information regulation 2 homolog 1, a gene upstream of PGC-1α, prevented aldosterone-induced mitochondrial damage and podocyte injury by upregulating PGC-1α at both the transcriptional and post-translational levels. Resveratrol, a SIRT1 activator, attenuated aldosterone-induced mitochondrial malfunction and podocyte injury in vitro and in aldosterone-infused mice in vivo. Hence, endogenous PGC-1α may be important for maintenance of mitochondrial function in podocytes under normal conditions. Activators of SIRT1, such as resveratol, may be therapeutically useful in glomerular diseases to promote and maintain PGC-1α expression and, consequently, podocyte integrity.
Authors:
Yanggang Yuan; Songming Huang; Wenyan Wang; Yingying Wang; Ping Zhang; Chunhua Zhu; Guixia Ding; Bicheng Liu; Tianxin Yang; Aihua Zhang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-30
Journal Detail:
Title:  Kidney international     Volume:  82     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-11-08     Completed Date:  2013-02-01     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  771-89     Citation Subset:  IM    
Affiliation:
Department of Nephrology, Nanjing Children's Hospital, Institute of Pediatrics, Nanjing Medical University, Nanjing, China.
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MeSH Terms
Descriptor/Qualifier:
Aldosterone*
Animals
Apoptosis* / drug effects
Cell Line
Cytoprotection
Disease Models, Animal
Enzyme Activation
Gene Expression Regulation
Genes, Reporter
Kidney Diseases / chemically induced,  genetics,  metabolism,  pathology,  prevention & control*
Mice
Mice, Inbred C57BL
Mineralocorticoid Receptor Antagonists / pharmacology
Mitochondria / drug effects,  metabolism*,  pathology,  virology
Podocytes / drug effects,  metabolism*,  pathology,  virology
Promoter Regions, Genetic
RNA Interference
Receptors, Mineralocorticoid / drug effects,  metabolism
Respiratory Syncytial Virus Infections / genetics,  metabolism,  virology
Respiratory Syncytial Viruses / pathogenicity
Sirtuin 1 / genetics,  metabolism
Stilbenes / pharmacology
Time Factors
Trans-Activators / genetics,  metabolism*
Transfection
Chemical
Reg. No./Substance:
0/Mineralocorticoid Receptor Antagonists; 0/Ppargc1a protein, mouse; 0/Receptors, Mineralocorticoid; 0/Stilbenes; 0/Trans-Activators; 52-39-1/Aldosterone; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirtuin 1; Q369O8926L/resveratrol
Comments/Corrections
Comment In:
Kidney Int. 2012 Oct;82(7):735-6   [PMID:  22975995 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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