title: Cigarette smoke affects keratinocytes SRB1 expression and localization via H2O2 production and HNE protein adducts formation.
abstract: 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.
authors.affiliation: Department of Mechanical and Structural Engineering, University of Trento, Trento, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sticozzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Belmonte
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arezzini
authors.forename: Concetta
authors.initials: C
authors.lastname: Gardi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maioli
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
authors.forename: Marzia
authors.initials: M
authors.lastname: Toscano
authors.forename: Henry Jay
authors.initials: HJ
authors.lastname: Forman
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
mesh_terms: D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D021381:Protein Transport / Q000187:drug effects; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012879:Skin Physiological Phenomena / Q000187:drug effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D014028:Tobacco Smoke Pollution; D002784:Cholesterol; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases