Peroxisome proliferator-activated receptor agonists prevent 25-OH-cholesterol induced c-jun activation and cell death.
Peroxisome proliferator-activated receptor agonists prevent 25-OH-cholesterol induced c-jun activation and cell death.
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DOI：
10.1186/1471-2210-1-10
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Liu LZ
中科院分区：
文献类型：
--
作者：
Chang JY;Liu LZ
胆固醇氧化物是胆固醇的氧化衍生物，已被证明可导致多种细胞类型的程序性细胞死亡。使用N9小胶质细胞，本研究旨在研究胆固醇氧化物在执行程序性细胞死亡之前诱导的分子事件。小胶质细胞对25-OH-胆固醇非常敏感，因此用5 μM 25-OH-胆固醇处理细胞2天后，细胞活力降低至对照组的5-10%。在25-OH-胆固醇诱导的细胞死亡之前，小胶质细胞中c-jun和磷酸化c-jun水平呈剂量和时间依赖性增加。相比之下，7-β-OH-胆固醇，这是相对无毒的小胶质细胞，不增加磷酸-c-jun水平。过氧化物酶体增殖物激活受体（PPARs）是一类在动脉粥样硬化形成中起重要作用的核受体。本研究的结果表明，PPAR激动剂如15 d-PGJ 2、吲哚美辛和WY 14643可以减弱胆固醇氧化物诱导的小胶质细胞中c-jun活化和细胞死亡。过氧化物酶体增殖物激活受体激动剂可能是有用的，在未来的发展药理学药物对胆固醇氧化诱导的细胞毒性。
Cholesterol oxides, the oxygenated derivatives of cholesterol, have been shown to cause programmed cell death in a variety of cell types. Using N9 microglia, this study was designed to investigate the molecular events induced by cholesterol oxides prior to the execution of programmed cell death. Microglia were very sensitive to 25-OH-cholesterol, such that a 2-day treatment of the cells with 5 μM 25-OH-cholesterol reduced cell viability to 5–10% of controls. There was a dose- and time-dependent increase in c-jun and phospho-c-jun levels in microglia prior to this 25-OH-cholesterol induced cell death. In contrast, 7-β-OH-cholesterol, which was relatively non-toxic to microglia, did not increase phospho-c-jun levels. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that have important roles in atherogenesis. Results from this study indicate that PPAR agonists such as 15d-PGJ2, indomethacin and WY14643 can attenuate cholesterol oxide induced c-jun activation and cell death in microglia. Peroxisome proliferator-activated receptor agonists may be useful in future development of pharmacological agents against cholesterol oxide induced cytotoxicity.