Dymkowska Dorota, Szczepanowska Joanna, Wieckowski Mariusz R, Wojtczak Lech
Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warsaw, Poland.
Biochim Biophys Acta. 2006 Feb;1763(2):152-63. doi: 10.1016/j.bbamcr.2005.12.009.
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.
微摩尔浓度的花生四烯酸以及少量的油酸，可降低体外培养的AS - 30D大鼠肝癌细胞的线粒体膜电位，并增加细胞呼吸。线粒体通透性转换孔的阻滞剂环孢菌素A可部分阻止这两种脂肪酸对细胞呼吸的解偶联作用。花生四烯酸可增加活性氧（ROS）的产生速率，而油酸则降低该速率。两种脂肪酸均可诱导AS - 30D细胞发生凋亡性细胞死亡，同时伴有细胞色素c从线粒体释放至胞质溶胶、半胱天冬酶 - 3的激活以及促凋亡蛋白Bax与线粒体的结合；花生四烯酸的诱导作用比油酸更强。强效抗氧化剂生育三烯酚可阻止花生四烯酸诱导的ROS增加，并保护细胞免受该脂肪酸诱导的凋亡。研究得出结论，花生四烯酸和油酸通过线粒体途径诱导AS - 30D肝癌细胞凋亡，但作用机制不同：花生四烯酸主要通过刺激ROS产生来诱导凋亡，而油酸可能通过激活线粒体通透性转换孔促进程序性细胞死亡。
