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Glutaredoxin 2 (Grx2) gene deletion induces early onset of age-dependent cataracts in mice.

Authors
  • 1
  • 2
  • 3
  • 4
  • 5
Type
Published Article
Journal
The Journal of biological chemistry
1083-351X
Publication Date
Volume
289
Issue
52
Pages
36125–36139
Identifiers
DOI: 10.1074/jbc.M114.620047
PMID: 25362663
Source
Medline
Keywords
  • Age-Related Cataract
  • Electron Transport System
  • Glutaredoxin 2
  • Oxidative Stress
  • α-Crystallin Protein

Abstract

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, 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 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.

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