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Effects of histone acetylation on superoxide dismutase 1 gene expression in the pathogenesis of senile cataract
Author(s) -
Qiu X.,
Rong X.,
Jiang Y.,
Li D.,
Lu Y.
Publication year - 2016
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2016.0255
Subject(s) - acetylation , cataracts , senile cataract , histone , microbiology and biotechnology , chromatin immunoprecipitation , western blot , biology , gene expression , medicine , chemistry , ophthalmology , biochemistry , promoter , gene
Purpose 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. Methods 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. Anterior lens capsule samples of cataract patients were obtained by continuous curvilinear capsulorhexis during cataract surgery. The intact lenses of normal New Zealand rabbits and B‐3 HLECs were also cultured for intervene experiment. Western blot assay, quantitative real‐time PCR, chromatin immunoprecipitation (CHIP)‐PCR assay, immunofluorescence, CCK‐8 and flow cytometry were applied to investigate the influence of histone acetylation on SOD1 expression. Results 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 −1,500, −1,200, 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. Conclusions Histone acetylation plays an essential role in the regulation of SOD1 expression and in the pathogenesis of senile cataracts.