| Bax inhibitor 1 regulates ER-stress-induced ROS accumulation through the regulation of cytochrome P450 2E1. | |
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MedLine Citation:
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PMID: 19339548 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study investigated the molecular mechanism by which Bax inhibitor 1 (BI1) abrogates the accumulation of reactive oxygen species (ROS) in the endoplasmic reticulum (ER). Electron uncoupling between NADPH-dependent cytochrome P450 reductase (NPR) and cytochrome P450 2E1 (P450 2E1) is a major source of ROS on the ER membrane. ER stress produced ROS accumulation and lipid peroxidation of the ER membrane, but BI1 reduced this accumulation. Under ER stress, expression of P450 2E1 in control cells was upregulated more than in BI1-overexpressing cells. In control cells, inhibiting P450 2E1 through chemical or siRNA approaches suppressed ROS accumulation, ER membrane lipid peroxidation and the resultant cell death after ER stress. However, it had little effect in BI1-overexpressing cells. In addition, BI1 knock down also increased ROS accumulation and expression of P450 2E1. In a reconstituted phospholipid membrane containing purified BI1, NPR and P450 2E1, BI1 dose-dependently decreased the production of ROS. BI1 bound to NPR with higher affinity than P450 2E1. Furthermore, BI1 overexpression reduced the interaction of NPR and P450 2E1, and decreased the catalytic activity of P450 2E1, suggesting that the flow of electrons from NPR to P450 2E1 can be modulated by BI1. In summary, BI1 reduces the accumulation of ROS and the resultant cell death through regulating P450 2E1. |
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Authors:
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Hyung-Ryong Kim; Geum-Hwa Lee; Eun Yi Cho; Soo-Wan Chae; Taeho Ahn; Han-Jung Chae |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cell science Volume: 122 ISSN: 0021-9533 ISO Abbreviation: J. Cell. Sci. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-02 Completed Date: 2009-06-11 Revised Date: 2011-10-14 |
Medline Journal Info:
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Nlm Unique ID: 0052457 Medline TA: J Cell Sci Country: England |
Other Details:
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Languages: eng Pagination: 1126-33 Citation Subset: IM |
Affiliation:
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Department of Dental Pharmacology, School of Dentistry, Wonkwang University, Iksan, Chonbuk, 570-749, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Regulatory Proteins
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genetics,
metabolism* Cell Death Cell Line, Tumor Chlorzoxazone / metabolism Cytochrome P-450 CYP2E1 / antagonists & inhibitors, genetics, metabolism* Endoplasmic Reticulum / drug effects, enzymology* Enzyme Inhibitors / pharmacology Humans Hydroxylation Kinetics Lipid Peroxidation Membrane Proteins / genetics, metabolism* NADPH-Ferrihemoprotein Reductase / metabolism Nitrophenols / metabolism Oxidative Stress* / drug effects RNA Interference RNA, Small Interfering / metabolism Reactive Oxygen Species / metabolism* Substrate Specificity Transfection |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/Enzyme Inhibitors; 0/Membrane Proteins; 0/Nitrophenols; 0/RNA, Small Interfering; 0/Reactive Oxygen Species; 0/TMBIM6 protein, human; 100-02-7/4-nitrophenol; 95-25-0/Chlorzoxazone; EC 1.14.14.1/Cytochrome P-450 CYP2E1; EC 1.6.2.4/NADPH-Ferrihemoprotein Reductase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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