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Lysophosphatidylcholine as a death effector in the lipoapoptosis of hepatocytes

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Author(s)
Myoung Sook HanSun Young ParkKoei ShinzawaSunshin KimKun Wook ChungJi-Hyun LeeChoon Hyuck KwonKwang-Woong LeeJoon-Hyoek LeeCheol Keun ParkWoo Jin ChungJae Seok HwangJi-Jing YanDong-Keun SongYoshihide TsujimotoMyung-Shik Lee
Keimyung Author(s)
Chung, Woo JinHwang, Jae Seok
Department
Dept. of Internal Medicine (내과학)
Journal Title
Journal of Lipid Research
Issued Date
2008
Volume
49
Issue
1
Keyword
fatty acidsphospholipase A2steatohepatitistriglycerideceramide
Abstract
The pathogenesis of nonalcoholic steatohepatitis (NASH) is unclear, despite epidemiological data implicating FFAs. We studied the pathogenesis of NASH using lipoapoptosis models. Palmitic acid (PA) induced classical apoptosis of hepatocytes. PA-induced lipoapoptosis was inhibited by acyl-CoA synthetase inhibitor but not by ceramide synthesis inhibitors, suggesting that conversion products other than ceramide are involved. Phospholipase A2 (PLA2) inhibitors blocked PA-induced hepatocyte death, suggesting an important role for PLA2 and its product lysophosphatidylcholine (LPC). Small interfering RNA for Ca2+-independent phospholipase A2 (iPLA2) inhibited the lipoapoptosis of hepatocytes. PA increased LPC content, which was reversed by iPLA2 inhibitors. Pertussis toxin or dominant-negative Gαi mutant inhibited hepatocyte death by PA or LPC acting through G-protein-coupled receptor (GPCR)/Gαi. PA decreased cardiolipin content and induced mitochondrial potential loss and cytochrome c translocation. Oleic acid inhibited PA-induced hepatocyte death by diverting PA to triglyceride and decreasing LPC content, suggesting that FFAs lead to steatosis or lipoapoptosis according to the abundance of saturated/unsaturated FFAs. LPC administration induced hepatitis in vivo. LPC content was increased in the liver specimens from NASH patients. These results demonstrate that LPC is a death effector in the lipoapoptosis of hepatocytes and suggest potential therapeutic values of PLA2 inhibitors or GPCR/Gαi inhibitors in NASH.
Keimyung Author(s)(Kor)
정우진
황재석
Publisher
School of Medicine
Citation
Myoung Sook Han et al. (2008). Lysophosphatidylcholine as a death effector in the lipoapoptosis of hepatocytes. Journal of Lipid Research, 49(1), 84–97. doi: 10.1194/jlr.M700184-JLR200
Type
Article
ISSN
0022-2275
DOI
10.1194/jlr.M700184-JLR200
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34153
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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