Palmitate-induced apoptosis in neonatal cardiomyocytes is not dependent on the generation of ROS

Palmitate-induced apoptosis in neonatal cardiomyocytes is not dependent on the generation of ROS
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DOI:
10.1152/ajpheart.00726.2001
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发表时间:
2002-02-01
影响因子:
4.8
通讯作者:
McMillin, JB
McMillin, JB
中科院分区:
医学2区
文献类型:
--
作者:
Hickson-Bick, DLM;Sparagna, GC;McMillin, JB

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饱和脂肪酸棕榈酸酯诱导新生大鼠心肌细胞凋亡。这种细胞凋亡与线粒体早期释放细胞色素c和随后的线粒体膜电位丧失有关。最近的报道表明,活性氧物种(ROS)在棕榈酸酯诱导的细胞凋亡中发挥了作用。我们研究了ROS在棕榈酸酯诱导的新生大鼠心肌细胞凋亡中的作用,没有发现ROS参与的证据。ROS的产生、一氧化氮的产生和核因子-kappaB的激活并没有比使用非凋亡性脂肪酸油酸盐的观察到的增加。事实上,在油酸盐处理的细胞中,ROS的产生明显更高。此外,抗氧化剂和ROS清除剂的存在并没有减弱棕榈酸酯对细胞凋亡的诱导作用。脂肪酸与白蛋白的比例从2:1到7:1的变化对ROS的缺失或细胞凋亡的程度没有影响。没有发现棕榈酸酯处理的细胞中氧化蛋白修饰增加的证据。我们的结果使我们得出结论,氧化应激在棕榈酸酯诱导的细胞凋亡中不起作用。
The saturated fatty acid palmitate induces apoptosis in neonatal rat cardiomyocytes. This apoptosis is associated with early mitochondrial release of cytochrome c and a subsequent loss of mitochondrial membrane potential. Recent reports implicate a role for reactive oxygen species (ROS) in palmitate-induced apoptosis. We studied the role of ROS in palmitate-induced apoptosis in the neonatal rat cardiomyocyte and report no evidence of ROS involvement. ROS production, nitric oxide production, and nuclear factor-kappaB activation were not increased above those observed using the nonapoptotic fatty acid oleate. Indeed, the production of ROS was significantly higher in cells treated with oleate. Furthermore, the presence of antioxidants and ROS scavengers did not attenuate the induction of apoptosis by palmitate. Variations in the fatty acid-to-albumin ratio from 2: 1 to 7: 1 had no effect on the absence of ROS production or on the extent of apoptosis. No evidence was found for an increase in oxidative protein modification in palmitate-treated cells. Our results lead us to conclude that oxidative stress does not play a role in palmitate-induced apoptosis.