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 irradi...

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Bibliographic Details
Published in:Photochemical & photobiological sciences 2010, Vol.9 (1), p.18-24
Main Authors: Zhong, Julia L., Edwards, Gavin P., Raval, Chintan, Li, Haibin, Tyrrell, Rex M.
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomaterials
Cell Line
Cell Membrane - drug effects
Cell Membrane - metabolism
Cell Membrane - radiation effects
Chemistry
Enzyme Induction - drug effects
Enzyme Induction - radiation effects
Fibroblasts - cytology
Fibroblasts - drug effects
Fibroblasts - metabolism
Fibroblasts - radiation effects
Heme - metabolism
Heme Oxygenase-1 - biosynthesis
Hemin - pharmacology
Humans
NF-E2-Related Factor 2 - metabolism
Physical Chemistry
Plant Sciences
Skin - cytology
Ultraviolet Rays
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Summary: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.
ISSN:1474-905X
1474-9092
DOI:10.1039/b9pp00068b