Abstract
BackgroundAge-related cataract (ARC) is a serious visual impairment disease, and its pathogenesis is unclear. This article aims to investigate the role of ROCK1 in the apoptosis of lens epithelial cells (LECs) in age-related cataracts.MethodsWe collect anterior capsule samples from normal people, patients with age-related cataracts, young mice and naturally aging cataract mice. The oxidative stress-induced apoptosis model was constructed by cultivating HLE-B3 cells with H2O2. MTT, Hoechst 33342, and TUNEL assay were performed to explore proliferation and apoptosis. HE assay was used to observe cell morphology. The gene and protein expression were assessed by quantitative real-time PCR, western blot, immunofluorescence, and immunohistochemical staining.ResultThe results from the clinic and mice experiments showed that the numbers of lens epithelial cells from cataract individuals were less than the control individuals. In vitro, the apoptotic cells were increased in lens epithelial cells under H2O2 treatment. The ROCK1 protein level increased in the lens epithelial cells from age-related cataract patients and the old mice, respectively. Meanwhile, the up-regulation of the ROCK1 gene was associated with H2O2-induced HLE-B3 cells apoptosis. MTT and apoptosis assay showed ROCK1 was necessary in mediating H2O2-induced lens epithelial cells apoptosis through ROCK1 over-expression and knockdown experiment, respectively. Further investigation showed that p53 protein levels had been increased during ROCK1-mediated apoptosis in response to H2O2. Besides, ROCK1 phosphorylated p53 at ser15 to up-regulate its protein level.ConclusionsThis study established the novel association of ROCK1/p53 signaling with lens epithelial cells apoptosis and age-related cataract genesis.
Highlights
Age-related cataract (ARC) is a serious visual impairment disease, and its pathogenesis is unclear
This study established the novel association of Rho-associated coiled-coil-containing protein kinase 1 (ROCK1)/p53 signaling with lens epithelial cells apoptosis and age-related cataract genesis
Our results showed that ROCK1 mediated the p53 phosphorylation ser15 to up-regulate its protein level
Summary
Age-related cataract (ARC) is a serious visual impairment disease, and its pathogenesis is unclear. Hu et al Mol Med (2020) 26:124 specific molecular mechanisms in its developing process are to find the causes of the disease and develop effective anti-cataract medications, and to prevent, delay, or even reverse the lens opacity, which can protect the patients’ visual function to the maximum and improve their quality of life. It has great theoretical and social significance in reducing patients’ and social burden. Specific cellular signaling pathways during oxidative stress-induced apoptosis of lens epithelial cells remain unclear
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