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

Authors
  • Wu, Hongli1
  • Yu, Yibo2
  • David, Larry3
  • Ho, Ye-Shih4
  • Lou, Marjorie F5
  • 1 From the School of Veterinary Medicine and Biomedical Sciences, Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68583, the Department of Pharmaceutical Sciences, College of Pharmacy, University of North Texas Health Science Center, Fort Worth, Texas 76107.
  • 2 From the School of Veterinary Medicine and Biomedical Sciences, Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68583, the Department of Ophthalmology, Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China.
  • 3 the Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239.
  • 4 the Institute of Environment Health Sciences, Wayne State University, Detroit, Michigan 48201, and.
  • 5 From the School of Veterinary Medicine and Biomedical Sciences, Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68583, the Department of Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska 698583 [email protected]
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Dec 26, 2014
Volume
289
Issue
52
Pages
36125–36139
Identifiers
DOI: 10.1074/jbc.M114.620047
PMID: 25362663
Source
Medline
Keywords
License
Unknown

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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