Trekli Marika C, Riss George, Goralczyk Regina, Tyrrell Rex M
Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
Free Radic Biol Med. 2003 Feb 15;34(4):456-64. doi: 10.1016/s0891-5849(02)01303-5.
The ultraviolet region of sunlight causes a significant oxidative stress to human skin cells and modulates expression of a series of genes in dermal fibroblasts and other cell types. The human heme oxygenase 1 (HO-1) gene is strongly activated within the first hours that follow UVA irradiation of normal human dermal fibroblasts (FEK4) and this response is being used as a marker of oxidative stress in cells. It has been shown that the induction of this gene occurs via singlet oxygen ((1)O(2)) produced upon interaction of UVA radiation with an as yet undefined cellular chromophore. Carotenoids, as the most potent singlet oxygen quenchers in nature, are expected to effectively suppress the UVA-induced HO-1 gene activation in human cells. In this study, we measured the suppression of UVA-induced levels of HO-1 mRNA after the addition of a series of six all-trans-beta-carotene concentrations (0.07, 0.2, 0.8, 2.3, 8.0, and 21 microM) to the culture medium of exponentially growing FEK4 cells. The corresponding levels of beta-carotene uptake and apo-carotenal formation were measured following HPLC separation. The results of this study show a concentration-dependent suppression of UVA- (250 kJ/m(2)) induced transcriptional activation of HO-1 in exponentially growing FEK4 cells by beta-carotene. Suppression occurred at concentrations that have been observed in human plasma after dietary supplementation with beta-carotene.
阳光中的紫外线区域会对人类皮肤细胞造成显著的氧化应激，并调节真皮成纤维细胞和其他细胞类型中一系列基因的表达。人类血红素加氧酶1（HO-1）基因在正常人真皮成纤维细胞（FEK4）受到UVA照射后的最初几个小时内会被强烈激活，这种反应被用作细胞氧化应激的标志物。研究表明，该基因的诱导是通过UVA辐射与一种尚未明确的细胞发色团相互作用产生的单线态氧（（1）O（2））介导的。类胡萝卜素作为自然界中最有效的单线态氧猝灭剂，有望有效抑制UVA诱导的人类细胞中HO-1基因的激活。在本研究中，我们向指数生长的FEK4细胞培养基中添加了六种全反式β-胡萝卜素浓度（0.07、0.2、0.8、2.3、8.0和21 microM），然后测量了UVA诱导的HO-1 mRNA水平的抑制情况。通过高效液相色谱分离后，测量了相应的β-胡萝卜素摄取水平和脱辅基类胡萝卜醛的形成。本研究结果表明，β-胡萝卜素对指数生长的FEK4细胞中UVA（250 kJ/m（2））诱导的HO-1转录激活具有浓度依赖性抑制作用。在饮食补充β-胡萝卜素后人体血浆中观察到的浓度下就出现了抑制作用。
