RESUMO
Ultraviolet (UV) exposure and atmospheric pollution are both independently implicated in skin diseases such as cancer and premature aging. UVA wavelengths, which penetrate in the deep layers of the skin dermis, exert their toxicity mainly through chromophore photosensitization reactions. Benzo[a]pyrene (BaP), the most abundant polycyclic aromatic hydrocarbon originating from the incomplete combustion of organic matter, could act as a chromophore and absorb UVA. We and other groups have previously shown that BaP and UVA synergize their toxicity in skin cells, which leads to important oxidation. Even if mitochondria alterations have been related to premature skin aging and other skin disorders, no studies have focused on the synergy between UV exposure and pollution on mitochondria. Our study aims to investigate the combined effect of UVA and BaP specifically on mitochondria in order to assess the effect on mitochondrial membranes and the consequences on mitochondrial activity. We show that BaP has a strong affinity for mitochondria and that this affinity leads to an important induction of lipid peroxidation and membrane disruption when exposed to UVA. Co-exposure to UVA and BaP synergizes their toxicity to negatively impact mitochondrial membrane potential, mitochondrial metabolism and the mitochondrial network. Altogether, our results highlight the implication of mitochondria in the synergistic toxicity of pollution and UV exposure and the potential of this toxicity on skin integrity.
Assuntos
Benzo(a)pireno , Peroxidação de Lipídeos , Mitocôndrias , Raios Ultravioleta , Raios Ultravioleta/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Benzo(a)pireno/toxicidade , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Pele/metabolismoRESUMO
Light and atmospheric pollution are both independently implicated in cancer induction and premature aging. Evidence has been growing more recently on the toxic synergy between light and pollutants. Polycyclic aromatic hydrocarbons (PAHs) originate from the incomplete combustion of organic matter. Some PAHs, such as the Benzo[a]pyrene (BaP), absorb ultraviolet A (UVA) wavelengths and can act as exogenous chromophores, leading to synergistic toxicity through DNA damage and cytotoxicity concomitant to ROS formation. In this study, we shed light on the mechanism underlying the toxic synergy between PAHs and UVA. Using dermal fibroblasts co-exposed to UVA and BaP, we have demonstrated that the photosensitization reaction causes mortality, which is most likely caused by ROS accumulation. We have shown that these ROS are concentrated in the lipids, which causes an important induction of lipid peroxidation and malondialdehyde, by-products of lipid peroxidation. We have also shown the accumulation of bulky DNA damage, most likely generated by these by-products of lipid peroxidation. To our knowledge, this study represents the first one depicting the molecular effects of photo-pollution on dermal skin.