The role of Nrf2 in ultraviolet A mediated heme oxygenase 1 induction in human skin fibroblasts.
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.
Zhong
Julia L
JL
Department of Pharmacy and Pharmacology, University of Bath, UK BA2 7AY.
Edwards
Gavin P
GP
Raval
Chintan
C
Li
Haibin
H
Tyrrell
Rex M
RM
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004790:Enzyme Induction / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D012867:Skin / Q000166:cytology*; D014466:Ultraviolet Rays
D051267:NF-E2-Related Factor 2; D006418:Heme; D006427:Hemin; D051547:Heme Oxygenase-1