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

doi:10.1039/b9pp00068b

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

Department of Life Sciences

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63 Citations (SciVal)

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 language	English
Pages (from-to)	18-24
Number of pages	7
Journal	Photochemical & Photobiological Sciences
Volume	9
Issue number	1
DOIs	https://doi.org/10.1039/b9pp00068b
Publication status	Published - Jan 2010

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10.1039/b9pp00068b

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title = "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.",

author = "Zhong, {J L} and Edwards, {G P} and C Raval and Li, {H B} and Tyrrell, {R M}",

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T1 - The role of Nrf2 in ultraviolet A mediated heme oxygenase 1 induction in human skin fibroblasts

AU - Zhong, J L

AU - Edwards, G P

AU - Raval, C

AU - Li, H B

AU - Tyrrell, R M

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

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

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REGULATION OF THE HUMAN HEME OXYGENASE 1 GENE BY SOLAR UVA R ADIATION - A POTENTIAL ROLE FOR BACH PROTEINS AND HEME TURNO

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

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REGULATION OF THE HUMAN HEME OXYGENASE 1 GENE BY SOLAR UVA R ADIATION - A POTENTIAL ROLE FOR BACH PROTEINS AND HEME TURNO

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