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

Hongli Wu, Yibo Yu, Larry David, Ye Shih Ho, Marjorie F. Lou

Research output: Contribution to journalArticle

24 Scopus citations

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 KOmice. Compared with theWTcontrol, the lens of Grx2 KO mice had only 50% of the activity in complex I and complex IV and less than 10% of theATPpool. 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.

Original languageEnglish (US)
Pages (from-to)36125-36139
Number of pages15
JournalJournal of Biological Chemistry
Volume289
Issue number52
DOIs
StatePublished - Dec 26 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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