Issue 1, 2010

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

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.

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

Article information

Article type
Paper
Submitted
24 Jul 2009
Accepted
08 Oct 2009
First published
28 Oct 2009

Photochem. Photobiol. Sci., 2010,9, 18-24

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. Li and R. M. Tyrrell, Photochem. Photobiol. Sci., 2010, 9, 18 DOI: 10.1039/B9PP00068B

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