Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Thiobarbituric Acid Reactive Substances Levels in Brain Tissue of Aldh2 Knockout Mice Following Ethanol Exposure for 8 Weeks

Aldh2 knockout 마우스에서 8주간 에탄올 노출에 따른 뇌조직의 thiobarbituric acid reactive substances 농도

  • Moon, Sun-In (Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University) ;
  • Eom, Sang-Yong (Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University) ;
  • Kim, Jung-Hyun (Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University) ;
  • Yim, Dong-Hyuk (Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University) ;
  • Kim, Hyong-Kyu (Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University) ;
  • Kim, Yong-Dae (Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University) ;
  • Kim, Heon (Department of Preventive Medicine, College of Medicine and Medical Research Institute, Chungbuk National University)
  • 문선인 (충북대학교 의과대학 예방의학교실) ;
  • 엄상용 (충북대학교 의과대학 예방의학교실) ;
  • 김정현 (충북대학교 의과대학 예방의학교실) ;
  • 임동혁 (충북대학교 의과대학 예방의학교실) ;
  • 김형규 (충북대학교 미생물학교실 및 의학연구소) ;
  • 김용대 (충북대학교 의과대학 예방의학교실) ;
  • 김헌 (충북대학교 의과대학 예방의학교실)
  • Received : 2011.05.17
  • Accepted : 2011.06.20
  • Published : 2011.08.30
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Abstract

Excessive alcohol consumption causes various degenerative brain diseases including Alzheimer's disease and Parkinson's disease. Absorbed ethanol is metabolized to acetaldehyde and acetic acid by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Acetaldehyde is well known as a toxicant through generation of reactive oxygen species (ROS). Therefore, ALDH2 activity may play important roles in the pathogenesis of alcohol-induced brain diseases. In this study, we demonstrated the effects of ALDH2 enzyme activity on lipid peroxidation in brain tissues and urine of mice exposed to ethanol for 8 weeks. Five male, 8-week old Aldh2 (+/+) and Aldh2 (-/-) mice (C57BL/6J strain) in each group were exposed to ethanol for 8 weeks (2 g/kg wt./day) using gavage, and those in the control group received 0.9% saline alone. Thiobarbituric acid reactive substances (TBARS) level, a marker for lipid peroxidation, was measured in whole brain tissue and urine by high performance liquid chromatography. As a result, chronic ethanol treatment did not show any statistical change on the TBARS level of brain tissue in both Aldh2 (+/+) mice and in Aldh2 (-/-) mice. However, following ethanol exposure for 8 weeks in Aldh2 (-/-) mice, the urinary TBARS levels were significantly increased to more than double compared to the pretreatment group. This result was not observed in Aldh2 (+/+) mice. These results suggest that although ALDH2 enzyme activity plays a role in the generation of ROS in the whole body, it does not seem to be important in the pathogenesis of alcohol induced degenerative brain diseases.

과다한 음주는 알츠하이머 및 파킨슨 질병과 같은 각종 만성 퇴행성 뇌질환의 대표적인 원인 중 하나로 알려져 있다. 체내에 유입된 에탄올은 알코올 탈수소효소(alcohol dehydrogenase, ADH)에 의해 아세트알데히드로 대사된 후 다시 알데히드탈수소효소 2(aldehyde dehydrogenase 2, ALDH2)에 의해 아세트산으로 대사되어 배출된다. 에탄올의 대사과정 중에는 다량의 free radical이 생성되어 체내에서 산화적 스트레스를 유발하는 것으로 알려져 있고, 아세트알데히드는 활성산소를 생산하는 독성물질로 잘 알려져 있다. 본 연구에서는 8주간 에탄올에 노출된 Aldh2 knockout 마우스를 사용하여 ALDH2 효소 활성이 뇌 조직과 소변의 지질과산화에 미치는 영향에 대하여 살펴보았으며, 지질과산화 정도를 측정하기 위해 HPLC를 통한 TBARS 정도를 측정하였다. 연구결과, 마우스에서 만성 에탄올 섭취는 뇌 조직 TBARS 생성에 영향을 주지 않는 것으로 나타났으나, 소변 TBARS는 Aldh2 (-/-) 마우스에서 에탄올을 투여함에 따라 유의한 증가를 보였다(p<0.05). 본 연구 결과로부터 8주간 에탄올을 경구 투여한 마우스에서 ALDH2의 활성은 체내의 전반적인 활성산소 생성에는 중요하게 관여하는 것으로 보이지만 뇌조직에서의 활성산소 생성에는 영향을 주지 않는 것으로 보이며, 이는 에탄올 노출과 이에 따른 활성산소가 다양한 만성 뇌질환을 유발한다는 기존의 가설에서 ALDH2의 활성이 중요하게 관여하지 않을 가능성을 시사한다.

Keywords

References

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