Document Detail


Cytochrome-P450 2B1 gene silencing attenuates puromycin aminonucleoside-induced cytotoxicity in glomerular epithelial cells.
MedLine Citation:
PMID:  20407477     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously, we demonstrated that cytochrome P450 2B1 (CYP2B1) can generate reactive oxygen species in puromycin aminonucleoside (PAN)-induced nephrotic syndrome, an animal model of minimal-change disease in humans. In this study we found that overexpression of CYP2B1 in rat glomerular epithelial cells in vitro significantly increased PAN-induced reactive oxygen species generation, cytotoxicity, cell death, and collapse of the actin cytoskeleton. All of these pathological changes were markedly attenuated by siRNA-induced CYP2B1 silencing. The cellular CYP2B1 protein content was significantly decreased whereas its mRNA level was markedly increased, suggesting regulation by protein degradation rather than transcriptional inhibition in the PAN-treated glomerular epithelial cells. This degradation of CYP2B1 was accompanied by the induction of heme oxygenase-1, an important indicator of heme-induced oxidative stress. In PAN-treated CYP2B1-silenced glomerular epithelial cells the induction of heme oxygenase-1 and caspase-3 activity were significantly decreased. Further, cleavage of the stress-induced pro-apoptotic endoplasmic reticulum-specific pro-caspase-12 was prevented in the silenced cells. Our results support a pivotal role of CYP2B1 for reactive oxygen species production in the endoplasmic reticulum in PAN-induced cytotoxicity.
Authors:
Niu Tian; Istvan Arany; David J Waxman; Radhakrishna Baliga
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-21
Journal Detail:
Title:  Kidney international     Volume:  78     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-30     Completed Date:  2010-12-02     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  182-90     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Cytochrome P-450 CYP2B1 / biosynthesis,  genetics*
Epithelial Cells / drug effects*
Gene Expression
Gene Silencing*
Kidney Glomerulus / cytology*,  drug effects*
Puromycin Aminonucleoside / toxicity*
Rats
Grant Support
ID/Acronym/Agency:
5 P42 ES07381/ES/NIEHS NIH HHS; P42 ES007381-15/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
58-60-6/Puromycin Aminonucleoside; EC 1.14.14.1/Cytochrome P-450 CYP2B1
Comments/Corrections

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