| Cytochrome-P450 2B1 gene silencing attenuates puromycin aminonucleoside-induced cytotoxicity in glomerular epithelial cells. | |
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MedLine Citation:
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PMID: 20407477 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Niu Tian; Istvan Arany; David J Waxman; Radhakrishna Baliga |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-21 |
Journal Detail:
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Title: Kidney international Volume: 78 ISSN: 1523-1755 ISO Abbreviation: Kidney Int. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-30 Completed Date: 2010-12-02 Revised Date: 2013-05-29 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
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Languages: eng Pagination: 182-90 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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5 P42 ES07381/ES/NIEHS NIH HHS; P42 ES007381-15/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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58-60-6/Puromycin Aminonucleoside; EC 1.14.14.1/Cytochrome P-450 CYP2B1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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