Skip to main content

Advertisement

SpringerLink
Log in

Oxidative stress and substance P mediate psychological stress-induced autophagy and delay of hair growth in mice

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Akar A, Arca E, Erbil H, Akay C, Sayal A, Gur AR (2002) Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata. J Dermatol Sci 29:85–90

    Article  CAS  PubMed  Google Scholar 

  2. Anisman H, Merali Z (2002) Cytokines, stress, and depressive illness. Brain Behav Immun 16:513–524

    Article  CAS  PubMed  Google Scholar 

  3. Ansel JC, Armstrong CA, Song I, Quinlan KL, Olerud JE, Caughman SW, Bunnett NW (1997) Interactions of the skin and nervous system. J Investig Dermatol Symp Proc 2:23–26

    Article  CAS  PubMed  Google Scholar 

  4. Aoki E, Shibasaki T, Kawana S (2003) Intermittent foot shock stress prolongs the telogen stage in the hair cycle of mice. Exp Dermatol 12:371–377

    Article  CAS  PubMed  Google Scholar 

  5. Arck PC, Handjiski B, Hagen E, Joachim R, Klapp BF, Paus R (2001) Indications for a ‘brain-hair follicle axis (BHA)’: inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P. FASEB J 15:2536–2538. doi:10.1096/fj.00-0699fje

    CAS  PubMed  Google Scholar 

  6. Arck PC, Handjiski B, Peters EM, Peter AS, Hagen E, Fischer A, Klapp BF, Paus R (2003) Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways. Am J Pathol 162:803–814. doi:10.1016/S0002-9440(10)63877-1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Arck PC, Slominski A, Theoharides TC, Peters EM, Paus R (2006) Neuroimmunology of stress: skin takes center stage. J Invest Dermatol 126:1697–1704. doi:10.1038/sj.jid.5700104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Askenase PW, Van Loveren H, Kraeuter-Kops S, Ron Y, Meade R, Theoharides TC, Nordlund JJ, Scovern H, Gerhson MD, Ptak W (1983) Defective elicitation of delayed-type hypersensitivity in W/Wv and SI/SId mast cell-deficient mice. J Immunol 131:2687–2694

    CAS  PubMed  Google Scholar 

  9. Bauer ME, Jeckel CM, Luz C (2009) The role of stress factors during aging of the immune system. Ann NY Acad Sci 1153:139–152. doi:10.1111/j.1749-6632.2008.03966.x

    Article  CAS  PubMed  Google Scholar 

  10. Beaujouan JC, Heuillet E, Petitet F, Saffroy M, Torrens Y, Glowinski J (1993) Higher potency of RP 67580, in the mouse and the rat compared with other nonpeptide and peptide tachykinin NK1 antagonists. Br J Pharmacol 108:793–800

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Canu N, Tufi R, Serafino AL, Amadoro G, Ciotti MT, Calissano P (2005) Role of the autophagic-lysosomal system on low potassium-induced apoptosis in cultured cerebellar granule cells. J Neurochem 92:1228–1242. doi:10.1111/j.1471-4159.2004.02956.x

    Article  CAS  PubMed  Google Scholar 

  12. Chen L, Schrementi ME, Ranzer MJ, Wilgus TA, Dipietro LA (2014) Blockade of mast cell activation reduces cutaneous scar formation. PLoS One 9:e85226. doi:10.1371/journal.pone.0085226

    Article  PubMed Central  PubMed  Google Scholar 

  13. Chiba S, Numakawa T, Ninomiya M, Richards MC, Wakabayashi C, Kunugi H (2012) Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 39:112–119. doi:10.1016/j.pnpbp.2012.05.018

    Article  CAS  PubMed  Google Scholar 

  14. Codogno P, Meijer AJ (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12(Suppl 2):1509–1518. doi:10.1038/sj.cdd.4401751

    Article  CAS  PubMed  Google Scholar 

  15. Dhabhar FS (2013) Psychological stress and immunoprotection versus immunopathology in the skin. Clin Dermatol 31:18–30. doi:10.1016/j.clindermatol.2011.11.003

    Article  PubMed  Google Scholar 

  16. Gu HF, Tang CK, Yang YZ (2012) Psychological stress, immune response, and atherosclerosis. Atherosclerosis 223:69–77. doi:10.1016/j.atherosclerosis.2012.01.021

    Article  CAS  PubMed  Google Scholar 

  17. Gutteridge JM (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41:1819–1828

    CAS  PubMed  Google Scholar 

  18. Hahn SM, Tochner Z, Krishna CM, Glass J, Wilson L, Samuni A, Sprague M, Venzon D, Glatstein E, Mitchell JB et al (1992) Tempol, a stable free radical, is a novel murine radiation protector. Cancer Res 52:1750–1753

    CAS  PubMed  Google Scholar 

  19. Huang J, Lam GY, Brumell JH (2011) Autophagy signaling through reactive oxygen species. Antioxid Redox Signal 14:2215–2231. doi:10.1089/ars.2010.3554

    Article  CAS  PubMed  Google Scholar 

  20. Hutchinson KM, McLaughlin KJ, Wright RL, Bryce Ortiz J, Anouti DP, Mika A, Diamond DM, Conrad CD (2012) Environmental enrichment protects against the effects of chronic stress on cognitive and morphological measures of hippocampal integrity. Neurobiol Learn Mem 97:250–260. doi:10.1016/j.nlm.2012.01.003

    Article  PubMed  Google Scholar 

  21. Joachim RA, Sagach V, Quarcoo D, Dinh QT, Arck PC, Klapp BF (2004) Neurokinin-1 receptor mediates stress-exacerbated allergic airway inflammation and airway hyperresponsiveness in mice. Psychosom Med 66:564–571. doi:10.1097/01.psy.0000132878.08780.93

    Article  CAS  PubMed  Google Scholar 

  22. Katayama M, Aoki E, Suzuki H, Kawana S (2007) Foot shock stress prolongs the telogen stage of the spontaneous hair cycle in a non-depilated mouse model. Exp Dermatol 16:553–560. doi:10.1111/j.1600-0625.2007.00558.x

    Article  PubMed  Google Scholar 

  23. Kawana S, Liang Z, Nagano M, Suzuki H (2006) Role of substance P in stress-derived degranulation of dermal mast cells in mice. J Dermatol Sci 42:47–54. doi:10.1016/j.jdermsci.2005.12.004

    Article  CAS  PubMed  Google Scholar 

  24. Kennedy PG, Rodgers J, Jennings FW, Murray M, Leeman SE, Burke JM (1997) A substance P antagonist, RP-67,580, ameliorates a mouse meningoencephalitic response to Trypanosoma brucei brucei. Proc Natl Acad Sci USA 94:4167–4170

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Klionsky DJ, Emr SD (2000) Autophagy as a regulated pathway of cellular degradation. Science 290:1717–1721

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Krause K, Foitzik K (2006) Biology of the hair follicle: the basics. Semin Cutan Med Surg 25:2–10. doi:10.1016/j.sder.2006.01.002

    Article  CAS  PubMed  Google Scholar 

  27. Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958

    Article  CAS  PubMed  Google Scholar 

  28. Linley JE, Ooi L, Pettinger L, Kirton H, Boyle JP, Peers C, Gamper N (2012) Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons. Proc Natl Acad Sci USA 109:E1578–E1586. doi:10.1073/pnas.1201544109

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Liu N, Wang LH, Guo LL, Wang GQ, Zhou XP, Jiang Y, Shang J, Murao K, Chen JW, Fu WQ, Zhang GX (2013) Chronic restraint stress inhibits hair growth via substance P mediated by reactive oxygen species in mice. PLoS One 8:e61574. doi:10.1371/journal.pone.0061574

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Maggi CA, Patacchini R, Rovero P, Giachetti A (1993) Tachykinin receptors and tachykinin receptor antagonists. J Auton Pharmacol 13:23–93

    Article  CAS  PubMed  Google Scholar 

  31. Muller-Rover S, Handjiski B, van der Veen C, Eichmuller S, Foitzik K, McKay IA, Stenn KS, Paus R (2001) A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol 117:3–15. doi:10.1046/j.0022-202x.2001.01377.x

    Article  CAS  PubMed  Google Scholar 

  32. Naziroglu M, Kokcam I (2000) Antioxidants and lipid peroxidation status in the blood of patients with alopecia. Cell Biochem Funct 18:169–173. doi:10.1002/1099-0844(200009)18:3<169:AID-CBF870>3.0.CO;2-T

    Article  CAS  PubMed  Google Scholar 

  33. Paus R, Botchkarev VA, Botchkareva NV, Mecklenburg L, Luger T, Slominski A (1999) The skin POMC system (SPS). Leads and lessons from the hair follicle. Ann NY Acad Sci 885:350–363

    Article  CAS  PubMed  Google Scholar 

  34. Paus R, Cotsarelis G (1999) The biology of hair follicles. N Engl J Med 341:491–497. doi:10.1056/NEJM199908123410706

    Article  CAS  PubMed  Google Scholar 

  35. Peskin AV, Winterbourn CC (2000) A microtiter plate assay for superoxide dismutase using a water-soluble tetrazolium salt (WST-1). Clin Chim Acta 293:157–166

    Article  CAS  PubMed  Google Scholar 

  36. Peters EM (2012) Psychological support of skin cancer patients. Br J Dermatol 167:105–110. doi:10.1111/j.1365-2133.2012.11094.x

    Article  PubMed  Google Scholar 

  37. Ravikumar B, Berger Z, Vacher C, O’Kane CJ, Rubinsztein DC (2006) Rapamycin pre-treatment protects against apoptosis. Hum Mol Genet 15:1209–1216. doi:10.1093/hmg/ddl036

    Article  CAS  PubMed  Google Scholar 

  38. Sahin E, Gümüşlü S (2007) Immobilization stress in rat tissues: alterations in protein oxidation, lipid peroxidation and antioxidant defense system. Comp Biochem Physiol C: Toxicol Pharmacol 144:342–347. doi:10.1016/j.cbpc.2006.10.009

    Google Scholar 

  39. Scandalios JG (2005) Oxidative stress: molecular perception and transduction of signals triggering antioxidant gene defenses. Braz J Med Biol Res 38:995–1014 (S0100-879X2005000700003)

    Article  CAS  PubMed  Google Scholar 

  40. Schallreuter KU, Moore J, Wood JM, Beazley WD, Gaze DC, Tobin DJ, Marshall HS, Panske A, Panzig E, Hibberts NA (1999) In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. J Investig Dermatol Symp Proc 4:91–96

    Article  CAS  PubMed  Google Scholar 

  41. Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 26:1749–1760. doi:10.1038/sj.emboj.7601623

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Schnackenberg CG, Wilcox CS (1999) Two-week administration of tempol attenuates both hypertension and renal excretion of 8-Iso prostaglandin f2alpha. Hypertension 33:424–428

    Article  CAS  PubMed  Google Scholar 

  43. Seo JS, Park JY, Choi J, Kim TK, Shin JH, Lee JK, Han PL (2012) NADPH oxidase mediates depressive behavior induced by chronic stress in mice. J Neurosci 32:9690–9699. doi:10.1523/JNEUROSCI.0794-12.2012

    Article  CAS  PubMed  Google Scholar 

  44. Silva RH, Abilio VC, Takatsu AL, Kameda SR, Grassl C, Chehin AB, Medrano WA, Calzavara MB, Registro S, Andersen ML, Machado RB, Carvalho RC, Ribeiro Rde A, Tufik S, Frussa-Filho R (2004) Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Neuropharmacology 46:895–903. doi:10.1016/j.neuropharm.2003.11.032

    Article  CAS  PubMed  Google Scholar 

  45. Singh LK, Pang X, Alexacos N, Letourneau R, Theoharides TC (1999) Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: a link to neurogenic skin disorders. Brain Behav Immun 13:225–239. doi:10.1006/brbi.1998.0541

    Article  CAS  PubMed  Google Scholar 

  46. Spencer LV, Callen JP (1987) Hair loss in systemic disease. Dermatol Clin 5:565–570

    CAS  PubMed  Google Scholar 

  47. Taguchi Y, Tsuyama K, Watanabe T, Wada H, Kitamura Y (1982) Increase in histidine decarboxylase activity in skin of genetically mast-cell-deficient W/Wv mice after application of phorbol 12-myristate 13-acetate: evidence for the presence of histamine-producing cells without basophilic granules. Proc Natl Acad Sci USA 79:6837–6841

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Theoharides TC, Donelan JM, Papadopoulou N, Cao J, Kempuraj D, Conti P (2004) Mast cells as targets of corticotropin-releasing factor and related peptides. Trends Pharmacol Sci 25:563–568. doi:10.1016/j.tips.2004.09.007

    Article  CAS  PubMed  Google Scholar 

  49. Wu HH, Hsiao TY, Chien CT, Lai MK (2009) Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat. J Biomed Sci 16:19. doi:10.1186/1423-0127-16-19

    Article  PubMed Central  PubMed  Google Scholar 

  50. Zafir A, Banu N (2009) Induction of oxidative stress by restraint stress and corticosterone treatments in rats. Indian J Biochem Biophys 46:53–58

    CAS  PubMed  Google Scholar 

  51. Zhang GX, Kimura S, Murao K, Shimizu J, Matsuyoshi H, Takaki M (2009) Role of neuronal NO synthase in regulating vascular superoxide levels and mitogen-activated protein kinase phosphorylation. Cardiovasc Res 81:389–399. doi:10.1093/cvr/cvn304

    Article  CAS  PubMed  Google Scholar 

  52. Zhang GX, Kimura S, Nishiyama A, Shokoji T, Rahman M, Abe Y (2004) ROS during the acute phase of Ang II hypertension participates in cardiovascular MAPK activation but not vasoconstriction. Hypertension 43:117–124. doi:10.1161/01.HYP.0000105110.12667.F8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work is supported by the National Nature Science Foundation of China (81270316), the Research Program of Soochow University (Q413400111).

Conflict of interest

No declare.

Author information

Authors and Affiliations

  1. 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

    Lei Wang & Wen-Qing Fu

  2. Department of Pathology, Medical College of Soochow University, 199 Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou, 215123, People’s Republic of China

    Ling-Ling Guo

  3. Department of Physiology, Medical College of Soochow University, 199 Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou, 215123, People’s Republic of China

    Lin-Hui Wang & Guo-Xing Zhang

  4. New Drug Screening Center, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People’s Republic of China

    Jing Shang

  5. Department of Clinical Laboratory, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Koji Murao

  6. Department of Surgery, Harrison International Peace Hospital, 2 Ren-Ming Road, Hengsui, 053000, People’s Republic of China

    Deng-Feng Chen

  7. Department of Dermatology, the Second Affiliated Hospital of Nangtong University, 6 Hai-Er Road, Nantong, 226001, People’s Republic of China

    Xiang-Hua Fan

Authors
  1. Lei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ling-Ling Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lin-Hui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guo-Xing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jing Shang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Koji Murao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Deng-Feng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiang-Hua Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wen-Qing Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Guo-Xing Zhang or Wen-Qing Fu.

Additional information

L. Wang, L. - L. Guo, L.- H. Wang these authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Guo, LL., Wang, LH. et al. Oxidative stress and substance P mediate psychological stress-induced autophagy and delay of hair growth in mice. Arch Dermatol Res 307, 171–181 (2015). https://doi.org/10.1007/s00403-014-1521-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-014-1521-3

Keywords

Search

Navigation