| First Author | Wu H | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 52 | Pages | 36125-39 |
| PubMed ID | 25362663 | Mgi Jnum | J:275332 |
| Mgi Id | MGI:6304126 | Doi | 10.1074/jbc.M114.620047 |
| Citation | Wu H, et al. (2014) Glutaredoxin 2 (Grx2) gene deletion induces early onset of age-dependent cataracts in mice. J Biol Chem 289(52):36125-39 |
| abstractText | Glutaredoxin 2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and it controls thiol/disulfide balance in cells. In this study, we investigated whether 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 knock-out (KO) mice and age-matched wild-type (WT) mice ages 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 cataracts was 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, alphaA-crystallin, and betaB2-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 mice 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. |
