Journal of dental hygiene science (치위생과학회지)

The Korean Society of Dental Hygiene Science (한국치위생과학회)
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Autophagy May Mediate Cellular Senescence by Nicotine Stimulation in Gingival Fibroblasts

  • Jun, Nu-Ri (Department of Public Health, General Graduate School, Dankook University) ;
  • Jang, Jong-Hwa (Department of Public Health, General Graduate School, Dankook University) ;
  • Lee, Jae-Young (Department of Public Health, General Graduate School, Dankook University) ;
  • Lee, Sang-Im (Department of Public Health, General Graduate School, Dankook University)
  • Received : 2022.08.24
  • Accepted : 2022.09.15
  • Published : 2022.09.30
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Abstract

Background: When cells are damaged by nicotine, cellular senescence due to oxidative stress accelerates. In addition, stress-induced inflammatory response and cellular senescence cause the accumulation of damaged organelles in cells, and autophagy appears to remove them. Conversely, when autophagy is reduced, harmful cell components accumulate, and aging is accelerated. This study aimed to determine the association between nicotine-induced cellular senescence and autophagy expression patterns in human gingival fibroblasts. Methods: Cells were treated with various concentrations of nicotine (0, 0.1, 0.5, 1, 2, and 5 mM) and 10 nM rapamycin was added to 1 mM nicotine to investigate the relationship between autophagy and cellular senescence. Cell viability was confirmed using WST-8 and the degree of cellular senescence was measured by SA-β-gal staining. The expression of the inflammatory proteins (COX-2 and iNOS) and autophagy markers (LC3-II, p62, and Beclin-1) was analyzed by western blotting. Results: The cell viability tended to decrease in a concentration-dependent manner. COX-2 showed no concentration-dependent expression and iNOS increased in the 0.5 mM nicotine treated group. The degree of cellular senescence was the highest in the 1 mM nicotine treatment group. In the group treated with rapamycin and nicotine, the conversion ratio of LC3-II to LC3-I was the highest, that of p62 was the lowest, and the level of Beclin-1 proteins was significantly increased. Furthermore, the degree of cellular senescence was reduced in the group in which rapamycin was added to nicotine compared to that in the group treated with nicotine alone. Conclusion: This study provides evidence that autophagy activated in an aging environment reduces cellular senescence to a certain some extent.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2022R1F1A1076563).

References

  1. Genco RJ, Borgnakke WS: Risk factors for periodontal disease. Periodontol 2000 62: 59-94, 2013. https://doi.org/10.1111/j.1600-0757.2012.00457.x
  2. Wang PL, Ohura K, Fujii T, et al.: DNA microarray analysis of human gingival fibroblasts from healthy and inflammatory gingival tissues. Biochem Biophys Res Commun 305: 970-973, 2003. https://doi.org/10.1016/s0006-291x(03)00821-0
  3. Cuff MJ, McQuade MJ, Scheidt MJ, Sutherland DE, Van Dyke TE: The presence of nicotine on root surfaces of periodontally diseased teeth in smokers. J Periodontol 60: 564-569, 1989. https://doi.org/10.1902/jop.1989.60.10.564
  4. Han YK, Lee IS, Lee SI: JAK/STAT pathway modulates on Porphyromonas gingivalis lipopolysaccharide- and nicotine-induced inflammation in osteoblasts. J Dent Hyg Sci 17: 81-86, 2017. https://doi.org/10.17135/jdhs.2017.17.1.81
  5. Chen JH, Ozanne SE, Hales CN: Methods of cellular senescence induction using oxidative stress. Methods Mol Biol 371: 179-189, 2007. https://doi.org/10.1007/978-1-59745-361-5_14
  6. Sung BK, Chung HY: Significances of molecular inflamm- ation and energy metabolism during aging. Cancer Prev Res 10: 6-17, 2005.
  7. Yi HS, Heo SK, Yun HJ, Choi JW, Jung JH, Park SD: Anti-oxidative and anti-inflammatory effects of Draconis Resina in mouse macrophage cells. Korea J Herbol 23: 179-192, 2008.
  8. Lee BY, Han JA, Im JS, et al.: Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell 5: 187-195, 2006. https://doi.org/10.1111/j.1474-9726.2006.00199.x
  9. Glick D, Barth S, Macleod KF: Autophagy: cellular and molecular mechanisms. J Pathol 221: 3-12, 2010. https://doi.org/10.1002/path.2697
  10. Young AR, Narita M, Ferreira M, et al.: Autophagy mediates the mitotic senescence transition. Genes Dev 23: 798-803, 2009. https://doi.org/10.1101/gad.519709
  11. Cuervo AM, Bergamini E, Brunk UT, Droge W, Ffrench M, Terman A: Autophagy and aging: the importance of maintaining "clean" cells. Autophagy 1: 131-140, 2005. https://doi.org/10.4161/auto.1.3.2017
  12. Kim MS, Yun JW, Park JH, et al.: Autophagy has a beneficial role in relieving cigarette smoke-induced apoptotic death in human gingival fibroblasts. Int J Med Sci 13: 357-364, 2016. https://doi.org/10.7150/ijms.14592
  13. Awan MU, Deng Y: Role of autophagy and its significance in cellular homeostasis. Appl Microbiol Biotechnol 98: 5319-5328, 2014. https://doi.org/10.1007/s00253-014-5721-8
  14. Kang SW, Park HJ, Ban JY, Chung JH, Chun GS, Cho JO: Effects of nicotine on apoptosis in human gingival fibroblasts. Arch Oral Biol 56: 1091-1097, 2011. https://doi.org/10.1016/j.archoralbio.2011.03.016
  15. Nociti FH Jr, Nogueira-Filho GR, Primo MT, et al.: The influence of nicotine on the bone loss rate in ligature-induced periodontitis. A histometric study in rats. J Periodontol 71: 1460-1464, 2000. https://doi.org/10.1902/jop.2000.71.9.1460
  16. Chen YJ, Lee SS, Huang FM, Chang YC: Effects of nicotine on differentiation, prostaglandin E2, and nitric oxide production in cementoblasts. J Dent Sci 10: 431-436, 2015. https://doi.org/10.1016/j.jds.2015.03.007
  17. Lee SI, Yu JS: NFATc mediates lipopolysaccharide and nicotine-induced expression of iNOS and COX-2 in human periodontal ligament cells. J Dent Hyg Sci 15: 753-760, 2015. https://doi.org/10.17135/jdhs.2015.15.6.753
  18. Chen YC, Shen SC, Lin HY, Tsai SH, Lee TJ: Nicotine enhancement of lipopolysaccharide/interferon-gamma-induced cytotoxicity with elevating nitric oxide production. Toxicol Lett 153: 191-200, 2004. https://doi.org/10.1016/j.toxlet.2004.01.014
  19. Dimri GP, Lee X, Basile G, et al.: A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92: 9363-9367, 1995. https://doi.org/10.1073/pnas.92.20.9363
  20. Sun L, Wang X, Gu T, et al.: Nicotine triggers islet β cell senescence to facilitate the progression of type 2 diabetes. Toxicology 441: 152502, 2020. https://doi.org/10.1016/j.tox.2020.152502
  21. Bove J, Martinez-Vicente M, Vila M: Fighting neurodegeneration with rapamycin: mechanistic insights. Nat Rev Neurosci 12: 437-452, 2011. https://doi.org/10.1038/nrn3068
  22. Foster KG, Fingar DC: Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony. J Biol Chem 285: 14071-14077, 2010. https://doi.org/10.1074/jbc.R109.094003
  23. Tang P, Hou H, Zhang L, et al.: Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats. Mol Neurobiol 49: 276-287, 2014. https://doi.org/10.1007/s12035-013-8518-3
  24. White E: Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer 12: 401-410, 2012. https://doi.org/10.1038/nrc3262