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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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