title: Glutaredoxin 2 (Grx2) gene deletion induces early onset of age-dependent cataracts in mice.
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.
authors.affiliation: 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.
authors.forename: Hongli
authors.initials: H
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Yu
authors.affiliation: the Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Larry
authors.initials: L
authors.lastname: David
authors.affiliation: the Institute of Environment Health Sciences, Wayne State University, Detroit, Michigan 48201, and.
authors.forename: Ye-Shih
authors.initials: YS
authors.lastname: Ho
authors.affiliation: 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 mlou1@unl.edu.
authors.forename: Marjorie F
authors.initials: MF
authors.lastname: Lou
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002386:Cataract / Q000235:genetics*; D003553:Cystine / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D017353:Gene Deletion; D054477:Glutaredoxins / Q000235:genetics*; D005978:Glutathione / Q000378:metabolism; D007903:Lens Capsule, Crystalline / Q000378:metabolism / Q000473:pathology; D008297:Male; D057507:Mice, 129 Strain; D018345:Mice, Knockout
chemical_list: D005136:Eye Proteins; C516009:Glrx2 protein, mouse; D054477:Glutaredoxins; D003553:Cystine; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D005978:Glutathione
keywords: Age-related Cataract; Electron Transport System; Glutaredoxin 2; Oxidative Stress; α-Crystallin Protein