Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Effects of Nicotine, Cotinine and Benzopyrene as Smoke Components on the Expression of Antioxidants in Human Bronchial Epithelial Cells

흡연성분 중 Nicotine, Cotinine, Benzopyrene이 인체 기관지 상피세포에서 항산화제의 발현에 미치는 영향

  • Kim, Yong Seok (Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University) ;
  • Lee, Jae Hyung (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Kim, Sang Heon (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Kim, Tae Hyung (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Sohn, Jang Won (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Yoon, Ho Joo (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Park, Sung Soo (Department of Internal Medicine, College of Medicine, Hanyang University) ;
  • Shin, Dong Ho (Department of Internal Medicine, College of Medicine, Hanyang University)
  • 김용석 (한양대학교 의과대학 생화학분자생물학교실) ;
  • 이재형 (한양대학교 의과대학 내과학교실) ;
  • 김상헌 (한양대학교 의과대학 내과학교실) ;
  • 김태형 (한양대학교 의과대학 내과학교실) ;
  • 손장원 (한양대학교 의과대학 내과학교실) ;
  • 윤호주 (한양대학교 의과대학 내과학교실) ;
  • 박성수 (한양대학교 의과대학 내과학교실) ;
  • 신동호 (한양대학교 의과대학 내과학교실)
  • Received : 2006.12.11
  • Accepted : 2007.01.26
  • Published : 2007.03.30
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Abstract

Background: Cigarette smoking is an important risk factor for chronic bronchitis and COPD. Airway epithelial cells exposed to cigarette smoke components such as nicotine, cotinine and benzopyrene can generate reactive oxygen species (ROS) and be subject to oxidative stress. This oxidative stress can induce the inflammatory response in the lung by the oxidant itself or by the release of proinflammatory cytokines. It has been reported that nicotine stimulates ROS, which are associated with NF-${\kappa}B$. Methods: Beas2B cells were treated with nicotine, cotinine and benzopyrene. RT PCR was used to measure the expression of several antioxidant factors using the total RNA from the Beas2B cells. The level of superoxide dismutase(CuZnSOD), thioredoxin, glutathione reductase expression was examined. Results: 0.5 to 4 hours after the benzopyrene, nicotine and cotinine theatments, the level of thioredoxin and glutathione reductase expression decreased. Longer exposure to these compounds for 24 to 72 hours inhibited the expression of most of these antioxidant factors. Conclusion: During exposure to smoke compounds, thioredoxin and glutathione reductase are the key antioxidant factors induced sensitively between 0.5 and 4 hours but the levels these antioxidants decrease between 24 hour and 72hours.

흡연물질로서 benzopyrene, nicotine 및 cotinine등은 기관지상피세포인 Beas2B에서 CuZnSOD, thioredoxin, glutathione reductase 등의 발현량에 영향을 주며 특히 thioredoxin 및 glutathione reductase의 발현량을 노출 후 30분에서 4시간 경과 시간대에 증가시켰다가 24시간 이후에는 억제하는 특징을 나타내었다. 상기한 흡연물질에 의한 항산화효소의 조절기전에는 전사인자인 NNF-${\kappa}B$가 관여하는 것으로 추정되었다.

Keywords

References

  1. Church T, Pryor WA. Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 1985;64:111-26 https://doi.org/10.2307/3430003
  2. Zang LY, Stone K, Pryor WA. Detection of free radicals in aqueous extracts of cigarette tar by electron spin resonance. Free Radic Biol Med 1990;8:275-9 https://doi.org/10.1016/0891-5849(90)90075-T
  3. Kinnula VL. Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases. Thorax 2005;60:693-700 https://doi.org/10.1136/thx.2004.037473
  4. Rahman I, Biswas SK, Kode A. Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol 2006;533:222-39 https://doi.org/10.1016/j.ejphar.2005.12.087
  5. Barr J, Sharma CS, Sarkar S, Wise K, Dong L, Periyakaruppan A, et al. Nicotine induces oxidative stress and activates nuclear transcription factor kappa B in rat mesencephalic cells. Mol Cell Biochem 2006. [Epub ahead of print]
  6. Iho S, Tanaka Y, Takauji R, Kobayashi C, Muramatsu I, Iwasaki H, et al. Nicotine induces human neutrophils to produce IL-8 through the generation of peroxynitrite and subsequent activation of NFkappaB. J Leukoc Biol 2003;74:942-51 https://doi.org/10.1189/jlb.1202626
  7. Di Stefano A, Caramori G, Oates T, Capelli A, Lusuardi M, Gnemmi I, et al. Increased expression of nuclear factor-kappaB in bronchial biopsies from smokers and patients with COPD. Eur Respir J 2000;220:556-63
  8. Briede JJ, Godschalk RW, Emans MT, De Kok TM, van Agen E, van Maanen J, et al. In vitro and in vivo studies on oxygen free radical and DNA adduct formation in rat lung and liver during benzo[a]pyrene metabolism. Free Radic Res 2004;38:995-1002 https://doi.org/10.1080/10715760400000976
  9. Soto-Otero R, Mendez-Alvarez E, Hermida-Ameijeiras A, Lopez-Real AM, Labandeira-Garcia JL. Effects of (-)-nicotine and (-)-cotinine on 6-hydroxydopamineinduced oxidative stress and neurotoxicity: relevance for Parkinson's disease. Biochem Pharmacol 2002;64:125-35 https://doi.org/10.1016/S0006-2952(02)01070-5
  10. Wei W, Kim Y, Boudreau N. Association of smoking with serum and dietary levels of antioxidants in adults: NHANES III, 1988-1994. Am J Public Health 2001;91:258-64
  11. Kinnula VL, Crapo JD. Superoxide dismutases in the lung and human lung diseases. Am J Respir Crit Care Med 2003;167:1600-19 https://doi.org/10.1164/rccm.200212-1479SO
  12. Mates JM, Sanchez-Jimenez F. Antioxidant enzymes and their implications in pathophysiologic processes. Front Biosci 1999;4:D339-45 https://doi.org/10.2741/Mates
  13. Nadeem A, Raj HG, Chhabra SK. Increased oxidative stress and altered levels of antioxidants in chronic obstructive pulmonary disease. Inflammation 2005; 29:23-32 https://doi.org/10.1007/s10753-006-8965-3
  14. Sato A, Hara T, Nakamura H, Kato N, Hoshino Y, Kondo N, et al. Thioredoxin-1 suppresses systemic inflammatory responses against cigarette smoking. Antioxid Redox Signal 2006;8:1891-6 https://doi.org/10.1089/ars.2006.8.1891
  15. Lakari E. Expression of oxidant and antioxidant enzymes in human lung and interstitial lung diseases. Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium 1 of the University Hospital of Oulu, on April 19th, 2002. p.1-86
  16. Solak ZA, Kabaroglu C, Cok G, Parildar Z, Bayindir U, Ozmen D, et al. Effect of different levels of cigarette smoking on lipid peroxidation, glutathione enzymes and paraoxonase 1 activity in healthy people. Clin Exp Med 2005;5:99-105 https://doi.org/10.1007/s10238-005-0072-5