Harrison D C, Lemasters J J, Herman B
Department of Cell Biology & Anatomy, School of Medicine, University of North Carolina, Chapel Hill 27599-7090.
Biochem Biophys Res Commun. 1991 Jan 31;174(2):654-9. doi: 10.1016/0006-291x(91)91467-q.
Previous studies have suggested that alterations in phospholipid composition of plasma membranes may underlie lethal cell injury due to hypoxic and ischemic injury. The present study was designed to determine if such alterations are due to the activation of a pH-dependent phospholipase A2. Loss of cell viability and phospholipase A2 activity measured by arachidonic acid release increased in parallel during metabolic inhibition with KCN and iodoacetate (chemical hypoxia). Acidosis (pH 6.5) and the phospholipase inhibitors, dibucaine and mepacrine, delayed loss of cell viability and release of arachidonic acid to a similar extent. These findings suggest that a pH-dependent phospholipase A2 causes alterations in plasma membrane phospholipid composition after ATP-depletion which contribute to lethal cell injury.
以往的研究表明，质膜磷脂成分的改变可能是缺氧和缺血性损伤导致致死性细胞损伤的基础。本研究旨在确定这种改变是否是由于pH依赖性磷脂酶A2的激活所致。在用氰化钾和碘乙酸（化学性缺氧）进行代谢抑制期间，细胞活力的丧失以及通过花生四烯酸释放测定的磷脂酶A2活性平行增加。酸中毒（pH 6.5）以及磷脂酶抑制剂丁卡因和米帕林在相似程度上延迟了细胞活力的丧失和花生四烯酸的释放。这些发现表明，pH依赖性磷脂酶A2在ATP耗竭后导致质膜磷脂成分的改变，这促成了致死性细胞损伤。
