Glutaredoxin 2 (Grx2) gene deletion induces early onset of age-dependent cataracts in mice.
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.
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.
the Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239.
the Institute of Environment Health Sciences, Wayne State University, Detroit, Michigan 48201, and.
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]
- Published Article
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
- Publication Date
Dec 26, 2014
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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The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/25362663