title: Down-regulation of GJA3 is associated with lens epithelial cell apoptosis and age-related cataract.
abstract: Lens epithelial cell apoptosis is regarded as the common molecular basis of the initiation and subsequent progression of cataract. Recent studies have shown that Oxidative radicals derived from H2O2 causes lens epithelial cell apoptosis, While much work still needs to be done to elucidate this important mechanism of lens epithelial cell apoptosis induced by H2O2. The present study investigated the effect of human lens epithelial cell (SRA01/04) apoptosis induced by H2O2 and the possible molecular mechanism involved. Our data in this report has validated that H2O2 is an effective inducer of lens epithelial cells apoptosis, with the concentrations of H2O2 (100 μM). Moreover, we revealed that the down regulation of the GJA3 gene was associated with H2O2-induced lens epithelial cells apoptosis. Over-expression of GJA3 gene restrained the lens epithelial cells apoptosis induced by H2O2. Furthermore, GJA3 V44 M mutation partly inhibited the capacity of GJA3 to suppress apoptosis induced by H2O2 in SRA01/04 cells, eliciting the critical role of GJA3 in H2O2-induced lens epithelial cells apoptosis. The in vivo results indicated that down-regulation of GJA3 in lens epithelial cells was associated with age-related cataract genesis. Data from this study established the association of GJA3 down regulation with lens epithelial cells apoptosis and age-related cataract genesis.
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Ophthalmology, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, Heilongjiang, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Xinzhu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China. Electronic address: yushuiyushui@sina.com.
authors.forename: Cuige
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Ophthalmology, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, Heilongjiang, China. Electronic address: 17140893@qq.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China. Electronic address: jswkysgc@126.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D002386:Cataract / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D017630:Connexins; C082917:GJA3 protein, human; D006861:Hydrogen Peroxide
keywords: Age-related cataract genesis; GJA3; H2O2; Lens epithelial cells apoptosis