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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Metallothionein isoform 2A expression is inducible and protects against ROS-mediated cell death in rotenone-treated HeLa cells
Biochemical Journal, Volume 395, No. 2, Year 2006
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Description
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 over-expressed 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-over-expressing 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. © 2006 Biochemical Society.
Authors & Co-Authors
Reinecke, Fimmie
South Africa, Potchefstroom
North-west University
Levanets, O.
South Africa, Potchefstroom
North-west University
Ukraine, Kyiv
Institute of Molecular Biology and Genetics National Academy of Sciences of Ukraine
Olivier, Yolanda
South Africa, Potchefstroom
North-west University
Louw, Roan
South Africa, Potchefstroom
North-west University
Semete, Boitumelo
South Africa, Potchefstroom
North-west University
Grobler, Anne F.
South Africa, Potchefstroom
North-west University
Hidalgo, Juan
Spain, Cerdanyola Del Valles
Instituto de Neurociencias, Universitat Autònoma de Barcelona
Smeitink, Jan A.M.
Netherlands, Nijmegen
Radboud University Medical Center
Olckers, Antonel
South Africa, Potchefstroom
North-west University
Van Der Westhuizen, F. H.
South Africa, Potchefstroom
North-west University
Statistics
Citations: 10
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1042/BJ20051253
ISSN:
02646021
Research Areas
Cancer
Genetics And Genomics