| Metallothionein isoform 2A expression is inducible and protects against ROS-mediated cell death in rotenone-treated HeLa cells. | |
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MedLine Citation:
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PMID: 16402917 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of MT (metallothionein) gene expression was investigated in rotenone-treated HeLa cells to induce a deficiency of NADH:ubiquinone oxidoreductase (complex I). Complex I deficiency leads to a diversity of cellular consequences, including production of ROS (reactive oxygen species) and apoptosis. HeLa cells were titrated with rotenone, resulting in dose-dependent decrease in complex I activity and elevated ROS production at activities lower than 33%. Expression of MT2A (MT isoform 2A), but not MT1A or MT1B RNA, was significantly inducible by rotenone (up to 7-fold), t-BHP (t-butyl hydroperoxide; 5-fold) and CdCl2 (50-fold), but not ZnCl2. Myxothiazol treatment did not elevate either ROS or MT2A levels, which supports a ROS-related mechanism for rotenone-induced MT2A expression. To evaluate the role of MT2A expression, MT2A and MT1B were overexpressed in HeLa cells and treated with rotenone. Compared with control and MT1B-overexpressing cells, ROS production was significantly lower and cell viability higher in MT2A-overexpressing HeLa cells when ROS production was enhanced by treatment with t-BHP. Mitochondrial membrane potential was noticeably less reduced in both MT-overexpressing cell lines. MT2A overexpression in rotenone-treated cells also significantly reduced or delayed apoptosis induction, as measured by caspase 3/7 activity and cytosolic nucleosome enrichment. We conclude that MT2A offers significant protection against the main death-causing consequences of rotenone-induced complex I deficiency in HeLa cells. Our results are in support of the protective role against oxidative stress ascribed to MTs and provide evidence that MT2A expression may be a beneficial downstream adaptive response in complex I-deficient cells. |
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Authors:
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Fimmie Reinecke; Oksana Levanets; Yolanda Olivier; Roan Louw; Boitumelo Semete; Anne Grobler; Juan Hidalgo; Jan Smeitink; Antonel Olckers; Francois H Van der Westhuizen |
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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: The Biochemical journal Volume: 395 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-03-27 Completed Date: 2006-04-18 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 405-15 Citation Subset: IM |
Affiliation:
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Division of Biochemistry, School for Chemistry and Biochemistry, North-West University, Potchefstroom 2531, South Africa. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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analysis Apoptosis / drug effects Cell Death / drug effects Cell Survival / drug effects Cells, Cultured Electron Transport Complex I / drug effects Electron Transport Complex III / drug effects Hela Cells Humans Membrane Potentials / drug effects Metallothionein / genetics, metabolism* Mitochondria / metabolism Protein Isoforms / genetics, metabolism RNA, Messenger / genetics, metabolism Reactive Oxygen Species / metabolism* Recombinant Proteins / metabolism Rotenone / pharmacology* Up-Regulation / drug effects* tert-Butylhydroperoxide / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Protein Isoforms; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/Recombinant Proteins; 56-65-5/Adenosine Triphosphate; 75-91-2/tert-Butylhydroperoxide; 83-79-4/Rotenone; 9038-94-2/Metallothionein; EC 1.10.2.2/Electron Transport Complex III; EC 1.6.5.3/Electron Transport Complex I |
| Comments/Corrections | |
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