Department of Pharmacy and Pharmacology, University of Bath, UK BA2 7AY.
Photochem Photobiol Sci. 2010 Jan;9(1):18-24. doi: 10.1039/b9pp00068b. Epub 2009 Oct 28.
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.
紫外线-A（UVA，320-380nm）辐射是一种氧化应激，可强烈诱导培养的人原代皮肤成纤维细胞（FEK4）中血红素加氧酶 1（HO-1）的表达。在这项研究中，我们表明 NF-E2 相关因子 2（Nrf2）蛋白在 FEK4 细胞受到 UVA 照射后积累，HO-1 强烈诱导。用针对 Nrf2 的特异性短发夹 RNA（siRNA）（siNrf2）下调 Nrf2 可大大消除 UVA 照射或血红素处理后 HO-1 的诱导，表明 Nrf2 的激活介导了这两种药物对 HO-1 的调节。此外，游离血红素水平的降低导致 UVA 诱导的 Nrf2 和 HO-1 蛋白水平的强烈降低，证实血红素在 UV 介导的应激反应中起重要作用。Nrf2 蛋白的敲低增强了 UVA 照射引起的膜损伤，表明 Nrf2 在这些细胞中具有至关重要的保护作用。
