Antioxidative properties of glutaredoxin 2 in the lens

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Abstract

Glutaredoxin (Grx) belongs to the oxidoreductase family that controls cellular redox homeostasis. The glutathione-dependent Grx has a typical CXXC motif at its active site for efficient antioxidative function, and contains cytosolic Grx1 and mitochondrial Grx2 isoforms found in the lens and other ocular tissues. Both Grx1 and Grx2 have dethiolase activity that can reduce oxidized thiols in proteins/enzymes and restore enzymes/proteins activities/functions. Grx2 has additional peroxidase activity that can eliminate reactive oxygen species to maintain redox balance in cells. Its ability to protect the mitochondrial function makes it an effective molecule in preventing cell apoptosis. Our studies have shown that knockout (KO) Grx2 gene in lens epithelial cells causes the cells to be less viable with high sensitivity to oxidative stress, leakage in mitochondrial membrane, low ability to detoxify H2O2, and apoptotic. Enrich Grx2 KO cells with native recombinant Grx2 protein can rescue the cells from oxidative damage and apoptosis. Grx2 KO cells show impaired complex I and complex IV functions with low ATP pool. Mice with Grx2 gene deletion develop age-related cataract much faster than that of the wild type control mice.

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