Upregulation of histone H3 caused by CRYAA may contribute to the development of age-related cataract

[摘要] Objective: Age-relate cataract (ARC) is a disease of the eyes with no effective drugs to prevent or treat patients.The aim of the present study is to determine whether histone H3, αA-crystallin (CRYAA), β-galactosidase (GLB1), andp53 are involved in the pathogenesis of ARC. Methods: A total of 99 anterior lens capsules (ALCs) of patients with ARCof various nuclear grades, ultraviolet models of ALCs, and two human lens epithelial cell lines (FHL-124 and SRA01/04)were used, and the expression of histone H3, CRYAA, GLB1, and p53 were detected by immunoblotting and reversetranscription and real time-quantitative polymerase chain reaction. The association between CRYAA with histone H3,GLB1, and p53 was assessed in FHL-124 and SRA01/04 cells following CRYAA overexpression. Results: Histone H3and p53 in ALCs of patients with ARC were up-regulated in a grade-dependent manner, and the expression ofCRYAA showed a positive association with histone H3, p53, and GLB1. In UV models of ALCs and human lensepithelial cell lines, the expression levels of histone H3, cell apoptosis factors (Bax/Bcl-2, cleaved caspase-3), andinflammation factors (interleukin-6, tumor necrosis factor-α) were all up-regulated. Furthermore, transfection ofCRYAA in FHL-124 cells induced overexpression of histone H3. Conclusion: CRYAA-mediated upregulation ofhistone H3 may be involved in the pathogenesis of ARC. p53 may also have a role in ARC development, but not viathe CRYAA-histone H3 axis. The results of the present study may assist in improving our understanding of thepathogenesis of ARC and in identifying potential targets for treatment.

[学科分类] 仪器

[关键词] Age-related cataract;Histone H3;αA-crystallin;Anterior lens capsules;Basement membrane