Short-term and long-term effects of fatty acids in rat hepatoma AS-30D cells: The way to apoptosis
Short-term and long-term effects of fatty acids in rat hepatoma AS-30D cells: The way to apoptosis
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DOI：
10.1016/j.bbamcr.2005.12.009
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发表时间：
2006-02-01
影响因子：
5.1
通讯作者：
Wojtczak, L
中科院分区：
文献类型：
--
作者：
Dymkowska, D;Szczepanowska, J;Wojtczak, L
花生四烯酸，在较小程度上，油酸在微摩尔浓度降低线粒体膜电位内AS-30 D大鼠肝癌细胞在体外培养，并增加细胞呼吸。两种脂肪酸对细胞呼吸的解偶联作用部分地被环孢菌素A阻止，环孢菌素A是线粒体通透性转换孔的阻断剂。花生四烯酸增加活性氧（ROS）的产生率，而油酸降低it. Two脂肪酸诱导AS-30 D细胞凋亡的细胞死亡，伴随着细胞色素c从线粒体释放到胞质溶胶中，caspase-3的激活和促凋亡Bax蛋白与线粒体的协会;花生四烯酸是一个更有力的诱导剂比油酸。Trolox是一种有效的抗氧化剂，可防止花生四烯酸诱导的ROS增加，并保护细胞免受这种脂肪酸引起的凋亡。它的结论是，花生四烯酸和油酸诱导AS-30 D肝癌细胞凋亡的线粒体途径，但不同的作用机制：花生四烯酸诱导凋亡主要是通过刺激ROS的产生，而油酸可能有助于程序性细胞死亡的线粒体通透性转换孔的激活。(c)2005 Elsevier B. V.保留所有权利。
Arachidonic acid and, to a smaller extent, oleic acid at micromolar concentrations decreased the mitochondrial membrane potential within AS-30D rat hepatoma cells cultivated in vitro and increased cell respiration. The uncoupling effect of both fatty acids on cell respiration was partly prevented by cyclosporin A, blocker of the mitochondrial permeability transition pore. Arachidonic acid increased the rate of reactive oxygen species (ROS) production, while oleic acid decreased it. Both fatty acids induced apoptotic cell death of AS-30D cells, accompanied by the release of cytochrome c from mitochondria to the cytosol, activation of caspase-3 and association of proapoptotic Bax protein with mitochondria; arachidonic acid being a more potent inducer than oleic acid. Trolox, a potent antioxidant, prevented ROS increase induced by arachidonic acid and protected the cells against apoptosis produced by this fatty acid. It is concluded that arachidonic and oleic acids induce apoptosis of AS-30D hepatoma cells by the mitochondrial pathway but differ in the mechanism of their action: Arachidonic acid induces apoptosis mainly by stimulating ROS production, whereas oleic acid may contribute to programmed cell death by activation of the mitochondrial permeability transition pore. (c) 2005 Elsevier B.V. All rights reserved.