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.
Highlights
Introductionhistone deacetylases (HDACs) inhibitors, which block the effects of HDAC, can enhance histone acetylation, thereby altering transcription[27]
Previous studies have reported that histone acetylation is generally found to be associated with gene activation[31], while silenced and repressed genes are thought to be stably hypoacetylated[32]
histone deacetylases (HDACs) inhibitors, histone acetyltransferases (HATs), HDACs, and HAT inhibitors, which are related to histone hyper- and hypoacetylation, have the effects of gene activation or repression[31]
Summary
HDAC inhibitors, which block the effects of HDAC, can enhance histone acetylation, thereby altering transcription[27]. Due to the intimate relationship between histone acetylation and gene expression, multiple HAT and HDAC inhibitors have been studied and even undergone clinical trials to attempt to disrupt the balance between HATs and HDACs27,29,30. No studies have been conducted to determine whether histone acetylation regulates SOD1 expression in senile cataracts and whether the regulation is associated with the development of cataracts. The present study was designed to explore histone acetylation and SOD1 expression changes in the lens epithelia of senile cataract cases and to illustrate the regulation effects of histone acetylation modification on SOD1 gene expression in the pathogenesis of senile cataracts
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