Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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4-Hydroxynonenal Induces Endothelial Apoptosis through Mitochondrial Depolarization

4-Hydroxynonenal의 미토콘드리아 탈분극을 통한 혈관 내피 세포의 세포사 유도기전

  • 강대연 (부산대학교 약학대학 약학과) ;
  • 이지영 (부산대학교 약학대학 약학과) ;
  • 김민선 (부산대학교 약학대학 약학과) ;
  • 김철홍 (부산대학교 약학대학 약학과) ;
  • 김형근 (부산대학교 약학대학 약학과) ;
  • 이선미 (부산대학교 약학대학 약학과) ;
  • 권영미 (부산대학교 약학대학 약학과) ;
  • 이재원 (부산대학교 약학대학 약학과) ;
  • 백형석 (부산대학교 유전공학연구소) ;
  • 유병팔 (텍사스주립대학 건강과학센터) ;
  • 정해영 (부산대학교 약학대학 약학과)
  • Published : 2008.11.30
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Abstract

The 4-Hydroxynonenal (HNE) affects vascular dysfunctions probably through the interruption of the cellular redox balance. To better understand vascular abnormalities resulting from the accumulation of HNE, we delineated mechanism by which mitochondrial apoptosis occurs in the YPEN-1 endothelial cells. HNE treatment led to the loss of mitochondrial membrane potential (${\delta}{\Psi}_m$), resulting in the release of cytochrome c. Data showed decreased Bcl-2 and increased Bax protein levels in HNE-treated cells. NAC, a reactive oxygen species (ROS) scavenger, and penicillamine, the peroxynitrite scavenger, blocked HNE-mediated ROS generation, thereby thwarting the cytochrome c release and apoptosis. The treatment of the cells with zVAD-fmk, a broad range caspase inhibitor did not suppress HNE-induced apoptosis, suggesting that the apoptosis might be the possibility of caspase-independent process. Our findings delineate the underlying mechanism of the HNE induced endothelial apoptosis by triggering depolarization of mitochondria membrane potential that can lead to the deterioration of vasculature homeostasis and subsequent vascular dysfunction with aging.

4-Hydroxynonenal (4-HNE)는 세포내 레독스의 균형을 깨뜨려 혈관 기능 손상을 일으킨다. 본 연구자들은 HNE의 축적이 야기하는 혈관 기능 손상기전을 더 잘 이해하기 위하여 혈관 내피 세포의 미토콘드리아 세포사 메커니즘을 규명하였다. HNE를 처리한 세포에서는 미토콘드리아 막전위 소실과 그에 따른 cytochrome C의 방출이 유도되었으며, Bax의 증가 및 Bcl-2의 감소가 관찰되었다. ROS 제거제인 NAC와 peroxynitrite 제거제인 페니실라민은 HNE가 유도하는 ROS 생성을 차단하여 cytochrome C 방출과 세포사를 억제하였다. 세포에 HNE와 zVAD-fmk (caspase 저해제)를 같이 처리하면 HNE가 유도하는 세포사를 억제하지 못하는데 이는 HNE에 의한 세포사가 caspase에 비의존적 단계일 가능성을 시사하였다. 위의 결과들은 HNE가 유도하는 혈관 내피 세포의 세포사 매커니즘은 미토콘드리아 막전위의 탈분극에 의해 촉발되며 이는 혈관계 항상성의 악화와 노화에 의해 수반되는 혈관기능 손상을 유도할 것으로 사료된다.

Keywords

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