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Guo-Tong Xu, Chunchun Zhuge, Jing-Ying Xu, Jingfa Zhang, Guoxu Xu, Lin Chen, Xiaoqing Liu, Hua Xu, Lixia Lu, Weiye Li; Fullerenol Protects RPE cells from Oxidative-stress Induced Premature Senescence via Activation of SIRT1. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4680.
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This study was aimed to study the protection and mechanisms of fullerenol on RPE cell senescence.
H2O2 pulse induced premature senescence in both aRPE-19 cell line and primary porcine RPE cells. Senescence-associated (SA) β-galactosidase staining, DNA damage analysis and cell cycle analysis was carried out to determine the protective function of fullerenol in RPE cell senescence. The redox status in aRPE-19 cells with or without fullerenol treatment was appraised by dichlorofluorescein (DCF) staining and catalase assay. The senescence and DNA damage related proteins were determined by western blot and immunofluorescence. The sirtuins activities were measured by sirtuin activity assay kit.
Fullerenol protected the RPE cells from H2O2-induced senescence through the blockage of p53 activation. H2O2 exposure triggered DNA damage signaling pathway including the acetylation of p53 at lysine 382. In coincidently, accumulated γ-H2Ax foci and phosphor-ATM were both increased in H2O2-induced senescence model. This reactive oxygen species induced DNA damage signaling pathway activation could be partially rescued by fullerenol treatment. Also, as an activator of SIRT1, fullerenol intervention finally inhibited p53 acetylation at K382, decreased p53 and its downstream target p21, which accumulated in senescence cells, in response to H2O2. The senescent protection of fullerenol could be neutralized by SIRT1 inhibitors. The well known SIRT1 activator, Resveratrol, showed the similar protection in senescence RPE cells as fullerenol
Fullerenol significantly attenuates RPE senescence induced by H2O2 through its anti-oxidant activity and promotes SIRT1 activity. SIRT1 mediated p53 deacetylation is pivotal in fullerenol anti-senescence mechanisms. Thus, this study suggests fullerenol as the anti-AMD molecular and indicates SIRT1 as the potential therapeutic target of AMD treatment.
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