The role of Nrf2 in ultraviolet A mediated heme oxygenase 1 induction in human skin fibroblasts

J L Zhong, G P Edwards, C Raval, H B Li, R M Tyrrell

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Ultraviolet-A (UVA, 320-380 nm) radiation is an oxidative stress that strongly induces heme oxygenase 1 (HO-1) expression in cultured human primary skin fibroblasts (FEK4). In this study, we show that NF-E2-related factor 2 (Nrf2) protein accumulates and HO-1 is strongly induced following UVA irradiation of FEK4 cells. Down-regulation of Nrf2 with specific short interfering RNA (siRNA) against Nrf2 (siNrf2) largely abolished the induction of HO-1 following either UVA irradiation or hemin treatment, suggesting that Nrf2 activation mediated modulation of HO-1 by both these agents. Furthermore, a reduction of free heme levels led to a strong decrease in UVA-induced Nrf2 and HO-1 protein levels confirming a clear role for heme in the UV-mediated stress response. Knock-down of Nrf2 protein enhanced membrane damage induced by UVA irradiation, indicating that Nrf2 has a crucial protective role in these cells.
Original languageEnglish
Pages (from-to)18-24
Number of pages7
JournalPhotochemical & Photobiological Sciences
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 2010

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