Fullerenol Protects Retinal Pigment Epithelial Cells From Oxidative Stress–Induced Premature Senescence via Activating SIRT1

• DOI: 10.1167/iovs.13-13732
• Publication Date: 2014-05-21T02:22:02Z
• Authors: Chun-Chun Zhuge; Jing-Ying Xu; Jingfa Zhang; Weiye Li; Peng Li; Zongyi Li; Ling Chen; Xiaoqing Liu; Peng Shang; Hua Xu; Yanjun Lu; Fang Wang; Lixia Lu; Guo-Tong Xu
• Keywords: Senescence

Oxidative stress-induced retinal pigment epithelium (RPE) senescence is one of the important factors in pathogenesis age-related macular degeneration (AMD). This study aimed to develop a new antisenescence-based intervention and clarify its possible molecular mechanism.A cell premature model was established both primary RPE cells ARPE-19 by exposure pulsed H₂O₂ stress for 5 days, confirmed with senescence-associated β-galactosidase (SA-β-gal) staining. The final concentration fullerenol (Fol) culture system μg/mL. Cellular redox status determined examination cellular reactive oxygen species (ROS) staining, catalase activity, ratio reduced oxidized glutathione, respectively. Deoxyribonucleic acid double-strand breaks were quantitative analysis γH₂AX. Cell cycle performed flow cytometry. SIRT1 activity examined Assay Kit. overexpression knockdown lentiviral-mediated infection.Pulsed triggered acetylation p53 at lysine 382 (K382) subsequent increase target p21(Waf1/Cip1). It also increased number accumulated phospho-γH2AX foci level phosphor-ATM cells. Fullerenol protected cells, as it positive SA-β-gal-staining alleviated depletion antioxidants, genomic DNA damage. Its mechanism might involve activation deacetylase SIRT1, resulting decreased levels acetyl-p53 roles protecting response Fol further applications activator (resveratrol) inhibitors (nicotinamide sirtinol), through knockdown.Fullerenol could rescue from oxidative antioxidation SIRT1. protective effect useful development strategies treat stress-related diseases like AMD.