Luo Jian, Shi Riyi
Department of Basic Medical Sciences, Institute for Applied Neurology, Center for Paralysis Research, Purdue University, West Lafayette, IN 47907, USA.
Neurochem Int. 2005 Feb;46(3):243-52. doi: 10.1016/j.neuint.2004.09.001. Epub 2004 Nov 14.
Acrolein, a byproduct of lipid peroxidation, has been shown to inflict significant structural and functional damage to isolated guinea pig spinal cord. Reactive oxygen species (ROS) are thought to mediate such detrimental effects. The current study demonstrates that acrolein can directly stimulate mitochondrial oxidative stress. Specifically, exposure of purified brain mitochondria to acrolein resulted in a dose-dependent increase of ROS and decreases in glutathione content and aconitase activity. This effect was not accompanied by significant intramitochondrial calcium influx or mitochondrial permeability transition, but rather by impaired function of the mitochondrial electron transport system. As well, we detected a significant inhibition of mitochondrial adenine nucleotide translocase (ANT) in the presence of acrolein. This inhibition of ANT likely contributes to acrolein-induced ROS elevation since application of atractyloside, a specific ANT inhibitor, induced significant increase of ROS. We hypothesize that inhibition of ANT may mediate, in part, the acrolein-induced ROS increase in mitochondria.
丙烯醛是脂质过氧化的一种副产物，已被证明会对分离出的豚鼠脊髓造成显著的结构和功能损伤。活性氧（ROS）被认为介导了这种有害作用。当前研究表明，丙烯醛可直接刺激线粒体氧化应激。具体而言，将纯化的脑线粒体暴露于丙烯醛会导致ROS呈剂量依赖性增加，同时谷胱甘肽含量和乌头酸酶活性降低。这种效应并未伴随着显著的线粒体内钙内流或线粒体通透性转换，而是由线粒体电子传递系统功能受损所致。此外，我们检测到在存在丙烯醛的情况下线粒体腺嘌呤核苷酸转位酶（ANT）受到显著抑制。ANT的这种抑制作用可能导致了丙烯醛诱导的ROS升高，因为应用特异性ANT抑制剂苍术苷会诱导ROS显著增加。我们推测，ANT的抑制可能部分介导了丙烯醛诱导的线粒体ROS增加。
