Malis C D, Bonventre J V
Massachusetts General Hospital, Boston 02114.
Prog Clin Biol Res. 1988;282:235-59.
In summary, with post ischemic and toxic injury, reactive oxygen species together with the Ca2+ activation of phospholipase A2, can produce injury to mitochondria. Reactive oxygen species damage mitochondria by enhancing membrane permeability and decreasing F1F0ATPase activity. With exposure of mitochondria to Ca2+ and reactive oxygen species, there is a synergistic injurious effect manifested by a marked increase in membrane permeability, a profound reduction in the electron transport chain respiratory function at site I, and a pronounced reduction in F1F0ATPase and adenine nucleotide translocase activities. Dibucaine, a PLA2 inhibitor, protected mitochondria exposed to Ca2+ and reactive oxygen species by preventing the electron transport defect, partially preserving F1F0ATPase activity, and restoring adenine nucleotide translocase activity to control levels. Mitochondrial function is important in generating ATP necessary for energy-dependent transport and restorative synthetic processes during the recovery state subsequent to ischemic or toxic injury. Understanding the cellular pathophysiology of ischemic and toxic mitochondrial damage will likely lead to the development of pharmacological approaches aimed at the enhancement of mitochondrial function and hence tissue survival and function after ischemic or toxic exposure.
总之，在缺血性和中毒性损伤后，活性氧与磷脂酶A2的Ca2+激活共同作用，可对线粒体造成损伤。活性氧通过增强膜通透性和降低F1F0ATP酶活性来损害线粒体。当线粒体暴露于Ca2+和活性氧时，会出现协同损伤效应，表现为膜通透性显著增加、位点I处电子传递链呼吸功能大幅降低以及F1F0ATP酶和腺嘌呤核苷酸转位酶活性明显降低。丁卡因是一种磷脂酶A2抑制剂，通过防止电子传递缺陷、部分保留F1F0ATP酶活性并将腺嘌呤核苷酸转位酶活性恢复到对照水平，从而保护暴露于Ca2+和活性氧的线粒体。线粒体功能对于在缺血或中毒性损伤后的恢复状态下产生能量依赖性转运和恢复性合成过程所需的ATP至关重要。了解缺血性和中毒性线粒体损伤的细胞病理生理学可能会促使开发旨在增强线粒体功能从而提高缺血或中毒暴露后组织存活率和功能的药理学方法。
