The role of SIRT1/AKT/ERK pathway in ultraviolet B induced damage on human retinal pigment epithelial cells

Wen Wen Chou, Ku Chung Chen, Yung Song Wang, Jaw Yuan Wang, Chung Ling Liang, Suh Hang Hank Juo

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1728-1736
Number of pages9
JournalToxicology in Vitro
Volume27
Issue number6
DOIs
Publication statusPublished - Sep 2013
Externally publishedYes

Keywords

  • AKT
  • Resveratrol
  • RPE
  • SIRT1
  • Ultraviolet B

ASJC Scopus subject areas

  • Toxicology

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