title: The role of SIRT1/AKT/ERK pathway in ultraviolet B induced damage on human retinal pigment epithelial cells.
abstract: Ultraviolet (UV)-induced damage plays a major role in ocular diseases, such as cataracts and retinal degeneration. UVB may also cause retinal phototoxicity and photic retinopathy. In this study, we explored the effects of UVB on the cell cycle and the role of silent mating type information regulation 2 homolog 1 (SIRT1) in the UVB-induced damage. UVB dose-dependently suppressed the growth of retinal pigment epithelial (RPE) cells by activating the phosphatidylinositol 3-kinase (PI3K) pathway and triggering cell cycle arrest at the S phase. SIRT1, an NAD-dependent histone deacetylase, is involved in multiple biological processes, such as the stress response and the regulation of the cell cycle. However, its role in the effects of UVB on RPE cells is unclear. We showed that UVB down-regulates SIRT1 expression in a dose-dependent manner. Resveratrol, an SIRT1 activator, prevented the UVB-induced damage by inhibiting AKT and ERK phosphorylation. A specific PI3K inhibitor attenuated the UVB-induced ERK1/2 and p53 phosphorylation. Finally, UVB activated the PI3K/AKT/ERK pathway by reducing the expression of SIRT1 in ARPE-19 cells. Our study, therefore, illustrated the molecular mechanisms of UVB-induced phototoxicity and damage of RPE cells. SIRT1 and resveratrol may be significant regulators, protecting against UVB-induced injury.
authors.affiliation: Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Chou
authors.forename: Ku-Chung
authors.initials: KC
authors.lastname: Chen
authors.forename: Yung-Song
authors.initials: YS
authors.lastname: Wang
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
authors.forename: Chung-Ling
authors.initials: CL
authors.lastname: Liang
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
mesh_terms: D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D015398:Signal Transduction / Q000528:radiation effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: 5-aza-2′-deoxycytidine; AKT; AZA; MAP kinases; PI3K; ROS; RPE; Resveratrol; SIRT1; Ultraviolet B; mitogen-activated protein (MAP) kinases; phosphatidylinositol-3-kinase; reactive oxygen species; retinal pigment epithelial