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Propofol protects human keratinocytes from oxidative stress via autophagy expression

  • Yoon, Ji-Young (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Jeon, Hyun-Ook (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Kim, Eun-Jung (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Kim, Cheul-Hong (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Yoon, Ji-Uk (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University) ;
  • Park, Bong-Soo (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Yu, Su-Bin (Department of Oral Anatomy, School of Dentistry, Pusan National University) ;
  • Kwak, Jin-Won (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute)
  • Received : 2017.02.01
  • Accepted : 2017.02.22
  • Published : 2017.03.30

Abstract

Background: The skin consists of tightly connected keratinocytes, and prevents extensive water loss while simultaneously protecting against the entry of microbial pathogens. Excessive cellular levels of reactive oxygen species can induce cell apoptosis and also damage skin integrity. Propofol (2,6-diisopropylphenol) has antioxidant properties. In this study, we investigated how propofol influences intracellular autophagy and apoptotic cell death induced by oxidative stress in human keratinocytes. Method: The following groups were used for experimentation: control, cells were incubated under normoxia (5% $CO_2$, 21% $O_2$, and 74% $N_2$) without propofol; hydrogen peroxide ($H_2O_2$), cells were exposed to $H_2O_2$ ($300{\mu}M$) for 2 h; propofol preconditioning (PPC)/$H_2O_2$, cells pretreated with propofol ($100{\mu}M$) for 2 h were exposed to $H_2O_2$; and 3-methyladenine $(3-MA)/PPC/H_2O_2$, cells pretreated with 3-MA (1 mM) for 1 h and propofol were exposed to $H_2O_2$. Cell viability, apoptosis, and migration capability were evaluated. Relation to autophagy was detected by western blot analysis. Results: Cell viability decreased significantly in the $H_2O_2$ group compared to that in the control group and was improved by propofol preconditioning. Propofol preconditioning effectively decreased $H_2O_2$-induced cell apoptosis and increased cell migration. However, pretreatment with 3-MA inhibited the protective effect of propofol on cell apoptosis. Autophagy was activated in the $PPC/H_2O_2$ group compared to that in the $H_2O_2$ group as demonstrated by western blot analysis and autophagosome staining. Conclusion: The results suggest that propofol preconditioning induces an endogenous cellular protective effect in human keratinocytes against oxidative stress through the activation of signaling pathways related to autophagy.

Keywords

References

  1. Proksch E, Folster-Holst R, Brautigam M, Sepehrmanesh M, Pfeiffer S, Jensen JM. Role of the epidermal barrier in atopic dermatitis. J Dtsch Dermatol Ges 2009; 7: 899-910.
  2. Schafer M, Werner S. Oxidative stress in normal and impaired wound repair. Pharmacol Res 2008; 58: 165-71. https://doi.org/10.1016/j.phrs.2008.06.004
  3. Dunham LJ. Cancer in man at site of prior benign lesion of skin or mucous membrane: a review. Cancer Res 1972; 32: 1359-74.
  4. Gulcin I, Alici HA, Cesur M. Determination of in vitro antioxidant and radical scavenging activities of propofol. Chem Pharm Bull 2005; 53: 281-5. https://doi.org/10.1248/cpb.53.281
  5. Wang B, Shravah J, Luo H, Raedschelders K, Chen DD, Ansley DM. Propofol protects against hydrogen peroxideinduced injury in cardiac H9c2 cells via Akt activation and Bcl-2 up-regulation. Biochem Biophys Res Commun 2009; 389: 105-11. https://doi.org/10.1016/j.bbrc.2009.08.097
  6. Jin YC, Kim W, Ha YM, Shin IW, Sohn JT, Kim HJ, et al. Propofol limits rat myocardial ischemia and reperfusion injury with an associated reduction in apoptotic cell death in vivo. Vascul Pharmacol 2009; 50: 71-7. https://doi.org/10.1016/j.vph.2008.10.002
  7. Svobodova A, Zdarilova A, Maliskova J, Mikulkova H, Walterova D, Vostalova J. Attenuation of UVA-induced damage to human keratinocytes by silymarin. J Dermatol Sci 2007; 46: 21-30. https://doi.org/10.1016/j.jdermsci.2006.12.009
  8. Andreassi M, Andreassi L. Antioxidants in dermocosmetology: from the laboratory to clinical application. J Cosmet Dermatol 2003; 2: 153-60. https://doi.org/10.1111/j.1473-2130.2004.00075.x
  9. Pillai S, Oresajo C, Hayward J. Ultraviolet radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation - a review. Int J Cosmet Sci 2005; 27: 17-34. https://doi.org/10.1111/j.1467-2494.2004.00241.x
  10. Syed DN, Malik A, Hadi N, Sarfaraz S, Afaq F, Mukhtar H. Photochemopreventive effect of pomegranate fruit extract on UVA-mediated activation of cellular pathways in normal human epidermal keratinocytes. Photochem Photobiol 2006; 82: 398-405. https://doi.org/10.1562/2005-06-23-RA-589
  11. Lippens S, Denecker G, Ovaere P, Vandenabeele P, Declercq W. Death penalty for keratinocytes: apoptosis versus cornification. Cell Death Differ 2005; 12: 1497-508. https://doi.org/10.1038/sj.cdd.4401722
  12. Kulms D, Schwarz T. Molecular mechanisms of UVinduced apoptosis. Photodermatol Photoimmunol Photomed. 2000; 16: 195-201. https://doi.org/10.1034/j.1600-0781.2000.160501.x
  13. Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 2004; 6: 463-77. https://doi.org/10.1016/S1534-5807(04)00099-1
  14. Corcoran TB, Engel A, Sakamoto H, O'Shea A, O'Callaghan-Enright S, Shorten GD. The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function. Br J Anaesth 2006; 97: 825-31. https://doi.org/10.1093/bja/ael270
  15. Murphy PG, Bennett JR, Myers DS, Davies MJ, Jones JG. The effect of propofol anaesthesia on free radicalinduced lipid peroxidation in rat liver microsomes. Eur J Anaesthesiol 1993; 10: 261-6.
  16. Wickley PJ, Shiga T, Murray PA, Damron DS. Propofol decreases myofilament Ca2+ sensitivity via a protein kinase C-, nitric oxide synthase-dependent pathway in diabetic cardiomyocytes. Anesthesiology 2006; 104: 978-87. https://doi.org/10.1097/00000542-200605000-00014
  17. Lakhani SA, Masud A, Kuida K, Porter GA Jr, Booth CJ, Mehal WZ, et al. Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science 2006; 311: 847- 51. https://doi.org/10.1126/science.1115035
  18. Cepero E, King AM, Coffey LM, Perez RG, Boise LH. Caspase-9 and effector caspases have sequential and distinct effects on mitochondria. Oncogene 2005; 24: 6354-66. https://doi.org/10.1038/sj.onc.1208793
  19. Sedlak TW, Oltvai ZN, Yang E, Wang K, Boise LH, Thompson CB, et al. Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. Proc Natl Acad Sci U S A. 1995; 92: 7834-8. https://doi.org/10.1073/pnas.92.17.7834
  20. Santoro MM, Gaudino G. Cellular and molecular facets of keratinocyte reepithelization during wound healing. Exp Cell Res 2005; 304: 274-86. https://doi.org/10.1016/j.yexcr.2004.10.033

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