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.

Evaluation of the antioxidant effects of different histone deacetylase inhibitors (HDACis) on human lens epithelial cells (HLECs) after UVB exposure

“…A previous study from our group found that the decrease of histone acetylation at the SOD1 promoter is associated with the decrease of SOD1 expression in age-related cataracts. Histone acetylation has an important role in regulating SOD1 expression which participate in the pathogenesis of age-related cataracts [9]. In our study, trichostatin A (TSA, an HDAC inhibitor) corrected the anacardic acid (AA, an HAT inhibitor)-induced imbalance between HATs and HDACs, resulting in enhancing SOD1 expression by reversing histone acetylation.…”

Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function

“…Oxidative stress Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry has long been accepted as an initiating factor in the aetiology of nuclear ARC [40]. Normal function of lenses depends on the balance among oxidative stress, antioxidant protection and repair processes [15,40]. Accumulation of reactive oxygen species (ROS) and/or the lack of nuclear glutathione (GSH) could induce apoptosis and lead to the development of nuclear ARC [5,41].…”

“…Critical enzymes involved in DNA methylation, such as DNMT1 and MeCP2, have been identified in human lens epithelial cells (HLECs) [10,11]. Epigenetic regulatory processes, including DNA methylation of CRYAA [9,10,[12][13][14], histone acetylation of SOD1 [15] and long non-coding RNA (lncRNA)-MIAT and KCNQ1OT1 [16,17], have been implicated in the pathological cataractogenesis.…”

Nuclear parameters and chromatin remodeling in epithelial cells and lymphocytes from the palpebral conjunctiva of dogs with keratoconjunctivitis sicca

“…The median values of STT1 were 25.00 mm/min (range, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] for the control group and 2.90 mm/min (range, 0-9) for the KCS group (P < .001). In relation to the TBUT, the median values were 10.00 seconds (range, 1-25) for the control group and 0.00 second (range, 0-8) for the KCS group (P < .001).…”

“…19,22,23 Senile cataract, diabetic retinopathy, macular degeneration, and autoimmune uveoretinitis are examples of diseases associated with remodeling of chromatin in ocular cells. [24][25][26][27][28][29] Nuclear size and shape, DNA content (ploidy), and chromatin remodeling can be studied in cytological preparations using video image analysis and the Feulgen reaction. 20,30 Video image analysis in Feulgen-stained preparations is recommended to evaluate defined cell populations.…”