title: Glutaredoxin 2 knockout increases sensitivity to oxidative stress in mouse lens epithelial cells.
abstract: Glutaredoxin belongs to the oxidoreductase family, with cytosolic glutaredoxin 1 (Grx1) and mitochondrial glutaredoxin 2 (Grx2) isoforms. Of the two isozymes, the function of Grx2 is not well understood. This paper describes the effects of Grx2 deletion on cellular function using primary lens epithelial cell cultures isolated from Grx2 gene knockout (KO) and wild-type (WT) mice. We found that both cell types showed similar growth patterns and morphology and comparable mitochondrial glutathione pool and complex I activity. Cells with deleted Grx2 did not show affected Grx1 or thioredoxin expression but exhibited high sensitivity to oxidative stress. Under treatment with H(2)O(2), the KO cells showed less viability, higher membrane leakage, enhanced ATP loss and complex I inactivation, and weakened ability to detoxify H(2)O(2) in comparison with the WT cells. The KO cells had higher glutathionylation in the mitochondrial proteins, particularly the 75-kDa subunit of complex I. Recombinant Grx2 deglutathionylated complex I and restored most of its activity. We conclude that Grx2 has a function that protects cells against H(2)O(2)-induced injury via its peroxidase and dethiolase activities; particularly, Grx2 prevents complex I inactivation and preserves mitochondrial function.
authors: Center of Redox Biology and School of Veterinary Medicine and Biomedical Sciences, University of Nebraska at Lincoln, NE 68583, USA.
authors: HongLi
authors: H
authors: Wu
authors: LiRen
authors: L
authors: Lin
authors: Frank
authors: F
authors: Giblin
authors: Ye-Sheh
authors: YS
authors: Ho
authors: Marjorie F
authors: MF
authors: Lou
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D054477:Glutaredoxins / Q000172:deficiency / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: C516009:Glrx2 protein, mouse; D054477:Glutaredoxins; D006861:Hydrogen Peroxide