SRB1 as a new redox target of cigarette smoke in human sebocytes

• Published in: Free radical biology & medicine Vol. 102; pp. 47 - 56
• Main Authors: Crivellari, Ilaria, Sticozzi, Claudia, Belmonte, Giuseppe, Muresan, Ximena M., Cervellati, Franco, Pecorelli, Alessandra, Cavicchio, Carlotta, Maioli, Emanuela, Zouboulis, Christos C., Benedusi, Mascia, Cervellati, Carlo, Valacchi, Giuseppe
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2017
• Subjects: Aldehydes - chemistry; Cholesterol - genetics; Cholesterol - metabolism; Cigarette Smoking - adverse effects; Coculture Techniques; Cutaneous tissue; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Humans; Hydroxynonenal; Keratinocytes - drug effects; Keratinocytes - metabolism; Lipids; Lipids - chemistry; Nicotiana - adverse effects; Nicotiana - chemistry; Oxidation-Reduction; Oxidative Stress - genetics; RNA, Small Interfering - genetics; Scavenger Receptors, Class B - genetics; Scavenger Receptors, Class B - metabolism; Smoke; Cutaneous tissue; Lipids; Hydroxynonenal; Smoke
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2016.11.021

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. [Display omitted] •Sebocytes are involved in maintaining skin functions.•Skin is the first barrier against outdoor insults.•Cigarette smoke (CS) affects skin homeostasis.•CS decreases SRB1 levels compromising sebocytes cholesterol uptake.•Lipids are essential to keep skin functionality.