Photosensitization Research Papers - Academia.edu (original) (raw)

UVA-driven photooxidative stress in human skin may originate from excitation of specific endogenous chromophores acting as photosensitizers. Previously, we have demonstrated that 3-hydroxypyridine-derived chromophores including B6-vitamers (pyridoxine, pyridoxamine, and pyridoxal) are endogenous photosensitizers that enhance UVA-induced photooxidative stress in human skin cells. Here, we report that the B6-vitamer pyridoxal is a micromolar sensitizer of genotoxic stress in human primary keratinocytes (HEKs) andreconstructed epidermis. Comparative array analysis indicated thatexposure to the combined action of pyridoxal and UVA caused upregulation of heat shock (HSPA6, HSPA1A, HSPA1L, HSPA2), redox (GSTM3, EGR1, MT2A, HMOX1, SOD1), and genotoxic (GADD45A, DDIT3, CDKN1A) stress response gene expression. Together with potentiation of UVA-induced photooxidative stress and glutathione depletion, induction of HEK cell death occurred only in response to the combined action of pyridoxal and UVA. In addition to activational phosphorylation indicative of genotoxic stress [p53 (Ser15) and γ- H2AX(Ser139)], comet analysis indicatedtheformation ofFpg-sensitiveoxidative DNA lesions, observable only aftercombined exposure to pyridoxal and UVA. In human reconstructed epidermis, pyridoxal pre-incubation followed by UVA exposure caused genomic oxidative base damage, procaspase 3 cleavage, and TUNEL-positivity, consistent with UVA-driven photooxidative damage that may be relevant to human skin exposed to high concentrations of B6-vitamers.