title: SRB1 as a new redox target of cigarette smoke in human sebocytes.
abstract: For its critical location, the skin represents the major interface between the body and the environment, therefore is one of the major biological barriers against the outdoor environmental stressors. Among the several oxidative environmental stressors, cigarette smoke (CS) has been associated with the development and worsening of many skin pathologies such as acne, dermatitis, delayed wound healing, aging and skin cancer. In our previous work we have demonstrated that CS is able to affect genes involved in skin cholesterol trafficking, among which SRB1, a receptor involved in the uptake of cholesterol from HDL, seems to be very susceptible to the oxidative stress induced by CS. In the present work we wanted to investigate the presence of SRB1 in human sebocytes and whether CS can affect cholesterol cellular uptake via the redox modulation of SRB1. By using a co-culture system of keratinocytes/sebocytes, we found that CS exposure induced a SRB1 protein loss without affecting sebocytes viability. The decrease of SRB1 levels was a consequence of SRB1/HNE adducts formation that leads to SRB1 ubiquitination and degradation. Moreover, the CS-induced loss of SRB1 induced an alteration of sebocytes lipid content, also demonstrated by cholesterol quantification in SRB1 siRNA experiments. In conclusion, exposure to CS, induced SRB1 post-translational modifications in sebocytes and this might affect sebocytes/skin functionality.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy; Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, Ferrara, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Crivellari
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sticozzi
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Belmonte
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Ximena M
authors.initials: XM
authors.lastname: Muresan
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Cervellati
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Cavicchio
authors.affiliation: Department of Life Sciences, University of Siena, Siena, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maioli
authors.affiliation: Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
authors.forename: Christos C
authors.initials: CC
authors.lastname: Zouboulis
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Mascia
authors.initials: M
authors.lastname: Benedusi
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, Ferrara, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cervellati
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy; Department of Animal Science, Plants for Human Health Institute, North Caroline State University, NC Research Campus, Kannapolis, NC, USA. Electronic address: giuseppe.valacchi@unife.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D000073865:Cigarette Smoking / Q000009:adverse effects*; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000378:metabolism; D014026:Nicotiana / Q000009:adverse effects / Q000737:chemistry
chemical_list: D000447:Aldehydes; D008055:Lipids; D034741:RNA, Small Interfering; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C462359:tert-4-hydroxy-2-nonenal; D002784:Cholesterol
keywords: Cutaneous tissue; Hydroxynonenal; Lipids; Smoke