TY - JOUR
T1 - Glutaredoxin 2 (Grx2) gene deletion induces early onset of age-dependent cataracts in mice
AU - Wu, Hongli
AU - Yu, Yibo
AU - David, Larry
AU - Ho, Ye Shih
AU - Lou, Marjorie F.
N1 - Publisher Copyright:
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.
PY - 2014/12/26
Y1 - 2014/12/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84919797503&partnerID=8YFLogxK
U2 - 10.1074/jbc.M114.620047
DO - 10.1074/jbc.M114.620047
M3 - Article
C2 - 25362663
AN - SCOPUS:84919797503
SN - 0021-9258
VL - 289
SP - 36125
EP - 36139
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 52
ER -