Scavenger Receptor B1 (SR-B1), also known as
HDL receptor, is involved in cellular
cholesterol uptake. Stratum corneum (SC), the outermost layer of the skin, is composed of more than 25%
cholesterol. Several reports support the view that alteration of SC
lipid composition may be the cause of impaired barrier function which gives rise to several
skin diseases. For this reason the regulation of the genes involved in
cholesterol uptake is of extreme significance for skin health. Being the first shield against external insults, the skin is exposed to several noxious substances and among these is cigarette
smoke (CS), which has been recently associated with various skin pathologies. In this study we first have shown the presence of SR-B1 in murine and human skin tissue and then by using immunoblotting, immunoprecipitation, RT-PCR, and confocal microscopy we have demonstrated the translocation and the subsequent lost of SR-B1 in human keratinocytes (cell culture model) after CS exposure is driven by
hydrogen peroxide (H(2)O(2)) that derives not only from the CS gas phase but mainly from the activation of cellular
NADPH oxidase (NOX). This effect was reversed when the cells were pretreated with NOX inhibitors or
catalase. Furthermore, CS caused the formation of SR-B1-aldheydes adducts (acrolein and 4-hydroxy-2-nonenal) and the increase of its ubiquitination, which could be one of the causes of SR-B1 loss. In conclusion, exposure to CS, through the production of H(2)O(2), induced post-translational modifications of SR-B1 with the consequence lost of the receptor and this may contribute to the skin physiology alteration as a consequence of the variation of
cholesterol uptake.