title: Oxidative stress and substance P mediate psychological stress-induced autophagy and delay of hair growth in mice.
abstract: Neuropeptide substance P (SP) and reactive oxygen species (ROS) have been demonstrated to play an important role in psychological stress-induced alteration of hair cycle, the underlying mechanism remains unknown. The present study aims to investigate possible contribution of SP and ROS in chronic restraint stress (CRS, a chronic psychological stress model) induced abnormal of hair cycle and induction of autophagy. Mouse CRS model was applied for 18 days with or without treatment antioxidant Tempol (a free radical scavenger) or SP receptor (NK1) antagonist (RP67580). After CRS procedure, hair growth cycle, oxidative stress markers and skin tissue autophagy levels were analyzed by ELISA or western blot. Our results revealed that CRS reduced body weight gain, distance of movement and times of standing, affected hair cycle by prolonging the telogen stage and delaying subsequent anagen and catagen stage. In addition, CRS resulted in increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and increase of autophagy markers (microtubule-associated proteins, light chain 3-II, LC3-II, and Beclin-1) in mice skin. Treatment with Tempol restored GSH-Px activity, and significantly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, as well as normalized hair cycle. In addition; RP67580 also restored SOD and GSH-Px activities, and markedly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, and normalized hair cycle. Our study provides the first strong evidence for SP and ROS play a role not only in alteration of hair cycle but also in induction of autophagy in psychological stress model, suggesting autophagy may contribute to psychological stress-induced abnormal of hair cycle.
authors.affiliation: Department of Clinical Psychology, Medical College of Soochow University, 199 Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou, 215123, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Guo
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Wang
authors.forename: Guo-Xing
authors.initials: GX
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.forename: Koji
authors.initials: K
authors.lastname: Murao
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Chen
authors.forename: Xiang-Hua
authors.initials: XH
authors.lastname: Fan
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Fu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001343:Autophagy; D015153:Blotting, Western / Q000379:methods; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005979:Glutathione Peroxidase / Q000378:metabolism; D006197:Hair / Q000254:growth & development*; D054833:Isoindoles; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D013113:Spin Labels; D013315:Stress, Psychological / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D054833:Isoindoles; D008869:Microtubule-Associated Proteins; D064729:Neurokinin-1 Receptor Antagonists; D013113:Spin Labels; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C001803:tempol