Beta-carotene suppresses UVA-induced HO-1 gene expression in cultured FEK4

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.