Scavenger Receptor B1 (SRB1), also known as HDL receptor, is involved in cellular cholesterol uptake. Stratum corneoum (SC), the outermost layer of the skin, is composed for more than 25% by cholesterol. Several reports support the view that alteration of SC lipids 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.

Due to its interface function between the body and the environment, the skin is chronically exposed to both endogenous and environmental pro-oxidant agents, leading to the harmful generation of reactive oxygen species (ROS) that can "physiologically" lead to increased lipid peroxidation products such as 4-hydroxy-2-nonenal. Using immunoblotting, immunoprecipitation, RT-PCR, and confocal microscopy we have demonstrated that the translocation and the consecutive lost of SRB1 in human keratinocytes is a consequence of increased lipid peroxidation (oxidative stress) which activated cellular NADPH oxidase (NOX). This effect was reversed when the cells were pretreated with NOX inhibitors, catalase, or superoxide dismutase (SOD) inhibitor. Furthermore, we have detected the formation of SRB1-aldheydes adducts (Acrolein and 4-Hydroxynonenal) and the increased of its ubiquitination that can contribute to the lost of SRB1. In conclusion, increased peroxidation levels as a consequence of oxidative stress condition induced post-translational modifications of SRB1 with the consequence decrease of the receptor and this can contribute to the skin physiology alteration.