Glutaredoxin2 (GRX2) gene deletion induced early on-set of age-dependent cataract in mice [Metabolism]

November 1st, 2014 by Wu, H., Yu, Y., David, L., Ho, Y.-S., Lou, M. F.

Glutaredoxin2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and controls thiol/disulfide balance in cells. In this study, we investigated if Grx2 gene deletion could induce faster age-related cataract formation and elucidated the biochemical changes effected by Grx2 gene deletion that may contribute to lens opacity. Slit lamp was used to examine the lenses in Grx2 knockout (KO) mice and age-matched wild-type (WT) mice aged from 1 to 16 months. In the Grx2 null mice, the lens nuclear opacity began at 5 months, 3 months sooner than that of the control mice and the progression of cataract were also much faster than the age-matched controls. Lenses of KO mice contained lower levels of protein thiols and GSH with a significant accumulation of S-glutathionylated proteins. Actin, αA-crystallin, and βB2-crystallin were identified by Western blot and mass spectroscopy as the major S-glutathionylated proteins in the lenses of 16 month-old Grx2 KO mice. Compared with the WT control, the lens of Grx2 KO mouse had only 50% of the activity in complex I, and complex IV, and less than 10% of the ATP pool. It was concluded that Grx2 gene deletion altered the function of lens structural proteins through S-glutathionylation, and also caused severe disturbance in mitochondrial function. These combined alterations affected lens transparency.