Veterinary and Biomedical Sciences, Department of
Date of this Version
8-1-2011
Citation
This is a PDF file of an unedited manuscript that has been accepted for publication.
Abstract
Glutaredoxin 2 (Grx2) belongs to the oxidoreductase family and is an isozyme of glutaredoxin 1 (Grx1) present in the mitochondria, however its function is not well understood. The purpose of this study is to evaluate the potential anti-apoptotic function of Grx2 by examining its ability to protect complex I in the mitochondrial electron transport system using human lens epithelial cells as a model. We found that cells treated with 200 μM hydrogen peroxide (H2O2) for 24 h exhibited decreased viability and became apoptotic with corresponding Bax up-regulation, Bcl-2 down-regulation, caspase 3 activation and mitochondrial cytochrome c leakage. Grx2 over-expression (OE) could protect cells against H2O2-induced damage while Grx2 knockdown (KD) showed the opposite effect. Under the same conditions, H2O2 treatment caused 50% inactivation of complex I activity in control cells (vector only), 75% in Grx2 KD cells but only 20% in Grx2 OE cells. This antiapoptotic function of Grx2 is specific as rotenone, a complex I specific inhibitor, could block this Grx2-mediated protection of complex I activity. Immunoprecipitation study also revealed that Grx2 co-precipitated with complex I in the mitochondrial lysate. Thus, the mechanism of Grx2 protection against H2O2- induced apoptosis is likely associated with its ability to preserve complex I.
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Biochemistry, Biophysics, and Structural Biology Commons, Cell and Developmental Biology Commons, Immunology and Infectious Disease Commons, Medical Sciences Commons, Veterinary Microbiology and Immunobiology Commons, Veterinary Pathology and Pathobiology Commons
Comments
Biochim Biophys Acta. 2010 October ; 1797(10): 1705–1715. doi:10.1016/j.bbabio.2010.06.003.