생명과학회지 (Journal of Life Science)

  • 제18권8호
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  • Pages.1173-1176
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  • 2008
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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ALDH2 효소의 활성이 알코올 섭취에 의한 8-hydroxydeoxyguanosine의 장기별 농도에 미치는 영향

Effect of ALDH2 Enzyme Activity on the Level of 8-Hydroxydeoxyguanosine in Tissues Following Ethanol Exposure

  • 장연위 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 최승희 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 김윤식 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 문선인 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 엄상용 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 김용대 (충북대학교 의과대학 예방의학교실 및 의학연구소) ;
  • 김헌 (충북대학교 의과대학 예방의학교실 및 의학연구소)
  • Zhang, Yan Wei (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Choi, Sheung-Hee (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Kim, Yun-Sik (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Moon, Sun-In (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Eom, Sang-Yong (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Kim, Yong-Dae (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University) ;
  • Kim, Heon (Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University)
  • 발행 : 2008.08.30
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초록

본 연구에서는 ALDH2 knockout 마우스를 이용하여 에탄올을 경구 투여한 후 간조직 및 뇌조직, 그리고 폐조직에서의 8-hydroxydeoxyguanosine (8-OHdG) 농도를 측정하여 각 장기에서의 산화적 유전자 손상정도를 평가하고 ALDH2 효소활성과의 관련성을 파악하였다. 간조직의 8-OHdG 농도는 에탄올 투여에 의해서도 유의하게 증가하지만 ALDH2 효소의 결핍이 더욱 큰 영향을 주는 것으로 확인되었다. 또한, 뇌조직과 폐조직의 8-OHdG 농도도 에탄올에 의해 모두 유의하게 증가하는 것으로 나타났으며 폐조직에서의 8-OHdG 농도는 ALDH2 효소의 활성에 따라 유의하게 영향을 받는 것으로 나타났다. 본 연구에서 에탄올의 반복적인 투여는 간조직 뿐 아니라 뇌조직과 폐조직에서도 산화적 유전자 손상을 유발하는 것으로 확인되었으며, 적어도 에탄올에 의한 간조직과 폐조직에서의 산화적 유전자 손상은 ALDH2 활성이 결핍된 경우에 더욱 커지는 것으로 조사되었다. 본 연구의 결과는 ALDH2 효소가 결핍된 사람에서 각종 암발생 위험도가 크게 나타나는 이유를 규명하는데 매우 중요한 근거자료로 활용될 수 있을 것으로 기대된다.

Individuals who regularly consume excessive quantities of alcohol are at a greater risk of developing various cancers such as esophageal, pharyngeal and lung cancers compared to normal populations if they are deficient in ALDH2 enzyme activity. We evaluated oxidative DNA damage in the liver, brain, and lung tissues of Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. The 8-hydroxydeoxyguanosine (8-OHdG) level in each tissue was evaluated as a biomarker of oxidative DNA damage. The 8-OHdG level in the liver, brain, and lung tissues was significantly increased following ethanol treatment. In addition, the level of 8-OHdG in the liver and lung tissues was affected by ALDH2 enzyme activity. This result suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated diseases, including cancer.

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참고문헌

  1. Agarwal, D. P. and H. W. Goedde. 1992. Pharmacogenetics of alcohol metabolism and alcoholism. Pharmacogenetics 2, 48-62 https://doi.org/10.1097/00008571-199204000-00002
  2. Aytacoglu, B. N., M. Calikoglu, L. Tamer, B. Coskun, N. Sucu, N. Kose, S. Aktas and M. Dikmengil. 2006. Alcoholinduced lung damage and increased oxidative stress. Respiration 73, 100-104 https://doi.org/10.1159/000088680
  3. Blanco, A. M. and C. Guerri. 2007. Ethanol intake enhances inflammatory mediators in brain: role of glial cells and TLR4/IL-1RI receptors. Front. Biosci. 1, 2616-2630
  4. Bondy, S. C. 1992. Ethanol toxicity and oxidative stress. Toxicol. Lett. 63, 231-241 https://doi.org/10.1016/0378-4274(92)90086-Y
  5. Bondy, S. C. and J. Orozco. 1994. Effects of ethanol treatment upon sources of reactive oxygen species in brain and liver. Alcohol 29, 375-383
  6. Brown, L. A., F. L. Harris, X. D. Ping and T. W. Gauthier. 2004. Chronic ethanol ingestion and the risk of acute lung injury: a role for glutathione availability? Alcohol 33, 191-197 https://doi.org/10.1016/j.alcohol.2004.08.002
  7. Enache, M., V. Van Waes, E. Vinner, M. Lhermitte, S. Maccari, and M. Darnaudery. 2008. Impact of an acute exposure to ethanol on the oxidative stress status in the hippocampus of prenatal restraint stress adolescent male rats. Brain Res. 29, 55-62
  8. Ishii, H., I. Kurose and S. Kato. 1997. Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress. J. Gastroenterol. Hepatol. 12, 272S-282S https://doi.org/10.1111/j.1440-1746.1997.tb00510.x
  9. Isse, T., K. Matsuno, T. Oyama, K. Kitagawa and T. Kawamoto. 2005. Aldehyde dehydrogenase 2 gene targeting mouse lacking enzyme activity shows high acetaldehyde level in blood, brain, and liver after ethanol gavages. Alcohol Clin. Exp. Res. 29, 1959-1964 https://doi.org/10.1097/01.alc.0000187161.07820.21
  10. Isse, T., T. Oyama, K. Kitagawa, K. Matsuno, A. Matsumoto and A. Yoshida. 2002. Diminished alcohol preference in transgenic mice lacking aldehyde dehydrogenase activity. Pharmacogenetics 12, 621-626 https://doi.org/10.1097/00008571-200211000-00006
  11. Kee, J. Y., M. O. Kim, I. Y. You, J. Y. Chai, E. S. Hong and S. C. An. 2003. Effects of genetic polymorphisms of ethanol- metabolizing enzymes on alcohol drinking behaviors. Taehan Kan Hakhoe Chi 9, 89-97
  12. Kim, Y. D., S. Y. Eom, M. Ogawa, T. Oyama, T. Isse, J. W. Kang, Y. W. Zhang, T. Kawamoto and H. Kim. 2007. Ethanol-induced oxidative DNA damage and CYP2E1 expression in liver tissue of Aldh2 knockout mice. J. Occup. Health 49, 363-369 https://doi.org/10.1539/joh.49.363
  13. Kim, Y. D., T. Oyama, T. Isse, H. Kim and T. Kawamoto. 2005. Expression levels of hepatic cytochrome P450 enzymes in Aldh2-deficient mice following ethanol exposure: a pilot study. Arch. Toxicol. 79, 192-195 https://doi.org/10.1007/s00204-004-0630-8
  14. Matsumoto, H. and I. Matsumoto. 2008. Alcoholism: protein expression profiles in a human hippocampal model. Expert Rev. Proteomics 5, 321-331 https://doi.org/10.1586/14789450.5.2.321
  15. Meier, P. and H. K. Seitz. 2008. Age, alcohol metabolism and liver disease. Curr. Opin. Clin. Nutr. Metab. Care 11, 21-26 https://doi.org/10.1097/MCO.0b013e3282f30564
  16. Nordmann, R., C. Ribiere and H. Rouach. 1992. Implication of free radical mechanisms in ethanol-induced cellular injury. Free Radic. Biol. Med. 12, 219-240 https://doi.org/10.1016/0891-5849(92)90030-K
  17. Oyama, T., T. Isse, N. Kagawa, T. Kinaga, Y. D. Kim and M. Morita. 2005. Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene-disruption on the expression of enzymes involved in alcohol metabolism. Front. Biosci. 10, 951-960 https://doi.org/10.2741/1589
  18. Reinke, L. A., Y. Kotake, P. B. McCay and E. G. Janzen. 1991. Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats: in vivo detection of 1-hydroxyethyl radicals with PBN. Free Radic. Biol. Med. 11, 31-39 https://doi.org/10.1016/0891-5849(91)90185-6
  19. Standridge, J. B. 2004. Pharmacotherapeutic approaches to the prevention of Alzheimer's disease. Am. J. Geriatr. Pharmacother. 2, 119-132 https://doi.org/10.1016/S1543-5946(04)90017-7
  20. Yokoyama, A., H. Watanabe, H. Fukuda, T. Haneda, H. Kato and T. Yokoyama. 2002. Multiple cancers associated with esophageal and oropharyngolaryngeal squamous cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese drinkers. Cancer Epidemiol. Biomarkers Prev. 11, 895-900
  21. Zhang, X, S. Y. Li, R. A. Brown and J. Ren. 2004. Ethanol and acetaldehyde in alcoholic cardiomyopathy: from bad to ugly en route to oxidative stress. Alcohol 32, 175-186 https://doi.org/10.1016/j.alcohol.2004.01.005

피인용 문헌

  1. Amyloid-β Levels in Mice Hippocampus According to the ALDH2 Enzyme Activity followed Ethanol Exposure for 8-Weeks vol.21, pp.11, 2011, https://doi.org/10.5352/JLS.2011.21.11.1636