title: Effects of histone acetylation on superoxide dismutase 1 gene expression in the pathogenesis of senile cataract.
abstract: Histone acetylation plays key roles in gene expression, but its effects on superoxide dismutase 1 (SOD1) expression in senile cataract remains unknown. To address this problem, the study was to investigate the influence of histone acetylation on SOD1 expression and its effects in the pathogenesis of senile cataract. Senile cataract was classified into three types-nuclear cataract (NC), cortical cataract (CC), and posterior subcapsular cataract (SC)-using the Lens Opacities Classification System III. In senile cataracts, SOD1 expression decreased significantly. Both H3 and H4 were deacetylated at -600 bp of the SOD1 promoter of cataract lenses, and hypoacetylated at -1500, -1200, and -900 bp. In hypoacetylated histones, the hypoacetylation pattern differed among the cataracts. In vitro, anacardic acid (AA) significantly reduced H3 and H4 acetylation at the SOD1 promoter, decreased protein expression, and induced cataract formation in rabbits. AA also inhibited HLEC viability and increased cell apoptosis. In contrast, trichostatin A (TSA) was able to efficaciously stop AA's effects on both rabbit lenses and HLECs. Decreased histone acetylation at the SOD1 promoter is associated with declined SOD1 expression in senile cataracts. Histone acetylation plays an essential role in the regulation of SOD1 expression and in the pathogenesis of senile cataracts.
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.|Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, China.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Rong
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.|Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.|Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.|Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.|Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.|Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, China.
authors.forename: Yinglei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.|Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D048729:Anacardic Acids / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D016022:Case-Control Studies; D002386:Cataract / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011817:Rabbits; D000072105:Superoxide Dismutase-1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D048729:Anacardic Acids; D006657:Histones; D006877:Hydroxamic Acids; C000606290:SOD1 protein, human; C088115:anacardic acid; C012589:trichostatin A; D000072105:Superoxide Dismutase-1