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Pathological Effect of Melatonin on Vascular Endothelial Cell Detachment

혈관내피세포 탈착에 미치는 melatonin의 병리학적 영향

  • Seo, Jeong-Hwa (Department of Molecular Biology & Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook University) ;
  • Kim, Sung-Hyen (Department of Molecular Biology & Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook University) ;
  • Ahn, Sun-Young (Department of Molecular Biology & Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook University) ;
  • Jeong, Eun-Sil (Department of Molecular Biology & Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook University) ;
  • Cho, Jin-Gu (Department of Molecular Biology & Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook University) ;
  • Park, Heon-Yong (Department of Molecular Biology & Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook University)
  • 서정화 (단국대학교 분자생물학과/BK21 RNA 전문인력양성팀/나노센서바이오텍연구소) ;
  • 김성현 (단국대학교 분자생물학과/BK21 RNA 전문인력양성팀/나노센서바이오텍연구소) ;
  • 안선영 (단국대학교 분자생물학과/BK21 RNA 전문인력양성팀/나노센서바이오텍연구소) ;
  • 정은실 (단국대학교 분자생물학과/BK21 RNA 전문인력양성팀/나노센서바이오텍연구소) ;
  • 조진구 (단국대학교 분자생물학과/BK21 RNA 전문인력양성팀/나노센서바이오텍연구소) ;
  • 박헌용 (단국대학교 분자생물학과/BK21 RNA 전문인력양성팀/나노센서바이오텍연구소)
  • Received : 2010.03.04
  • Accepted : 2010.04.20
  • Published : 2010.06.30

Abstract

In this study, we carried out a series of experiments to know whether melatonin, an anti-oxidative and immunosuppressive agent, played an important role in endothelial cells. It was revealed that melatonin had little or no effect on endothelial proliferation, cell death or migration. Additionally, melatonin had no effect on adhesion of THP-1 leukocytes to bovine aortic endothelial cells (BAECs) and THP-1 homotypic cell aggregation. In contrast, it was shown that melatonin diminished the basal level of nitric oxide by PP2A-mediated dephosphorylation of endothelial nitric oxide synthase (eNOS), leading to enhanced detachment of BAEC from the extracellular matrix. Collectively, melatonin in high doses decreases the NO production via regulations of PP2A and eNOS activities, inducing detachment of endothelial cells, a possible initial step for thrombosis.

항산화 기능과 면역 억제 기능을 갖는 것으로 알려진 melatonin이 혈관 내피층에서는 어떤 기능을 갖는지 알기 위한 일련의 실험을 수행하였다. 본 연구의 실험 결과, 혈관기능과 관련된 혈관내피세포의 성장, 사멸, 이동에 melatonin은 특이적인 효과를 나타내지 않았고, 백혈구의 혈관내피세포 부착과 백혈구 동종간의 응집에도 melatonin의 역할이 관찰되지 않았다. 이와는 대조적으로 melatonin은 PP2A를 통해 eNOS의 활성을 억제하여 산화질소의 양을 감소시키고, 이로 인해 혈관내피세포의 탈착이 유발되는 효과가 있음을 확인할 수 있었다. 종합해보면, 혈액 내 고농도의 melatonin은 PP2A 및 eNOS의 활성을 변화시켜 혈관내피세포의 탈착을 상승시킴으로써 혈관내에서 발생할 수 있는 혈전 형성에 의한 병리적 현상을 유발할 수 있다.

Keywords

References

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