Farooqui A A, Yang H C, Rosenberger T A, Horrocks L A
Department of Medical Biochemistry, Ohio State University, Columbus 43210, U.S.A.
J Neurochem. 1997 Sep;69(3):889-901. doi: 10.1046/j.1471-4159.1997.69030889.x.
Phospholipase A2 (PLA2) is the name for the class of lipolytic enzymes that hydrolyze the acyl group from the sn-2 position of glycerophospholipids, generating free fatty acids and lysophospholipids. The products of the PLA2-catalyzed reaction can potentially act as second messengers themselves, or be further metabolized to eicosanoids, platelet-activating factor, and lysophosphatidic acid. All of these are recognized as bioactive lipids that can potentially alter many ongoing cellular processes. The presence of PLA2 in the central nervous system, accompanied by the relatively large quantity of potential substrate, poses an interesting dilemma as to the role PLA2 has during both physiologic and pathologic states. Several different PLA2 enzymes exist in brain, some of which have been partially characterized. They are classified into two subtypes, Ca2+-dependent and Ca2+-independent, based on their catalytic dependence on Ca2+. Under physiologic conditions, PLA2 may be involved in phospholipid turnover, membrane remodeling, exocytosis, detoxification of phospholipid peroxides, and neurotransmitter release. However, under pathological situations, increased PLA2 activity may result in the loss of essential membrane glycerophospholipids, resulting in altered membrane permeability, ion homeostasis, increased free fatty acid release, and the accumulation of lipid peroxides. These processes, along with loss of ATP, may be responsible for the loss of membrane phospholipid and subsequent neuronal injury found in ischemia, spinal cord injury, and other neurodegenerative diseases. This review outlines the current knowledge of the PLA2 found in the central nervous system and attempts to define the role of PLA2 during both physiologic and pathologic conditions.
磷脂酶A2（PLA2）是一类脂解酶的统称，这类酶可从甘油磷脂的sn-2位水解酰基，生成游离脂肪酸和溶血磷脂。PLA2催化反应的产物本身可能作为第二信使，或者进一步代谢为类二十烷酸、血小板活化因子和溶血磷脂酸。所有这些都被认为是生物活性脂质，可能会改变许多正在进行的细胞过程。PLA2存在于中枢神经系统中，且伴有相对大量的潜在底物，这就引发了一个有趣的难题，即PLA2在生理和病理状态下所起的作用。大脑中存在几种不同的PLA2酶，其中一些已得到部分表征。根据它们对钙离子的催化依赖性，可将它们分为两种亚型，即钙离子依赖性和非钙离子依赖性。在生理条件下，PLA2可能参与磷脂周转、膜重塑、胞吐作用、磷脂过氧化物的解毒以及神经递质释放。然而，在病理情况下，PLA2活性增加可能导致必需的膜甘油磷脂丢失，从而导致膜通透性改变、离子稳态失衡、游离脂肪酸释放增加以及脂质过氧化物积累。这些过程，连同ATP的丧失，可能是缺血、脊髓损伤和其他神经退行性疾病中膜磷脂丢失及随后神经元损伤的原因。本综述概述了目前对中枢神经系统中PLA2的认识，并试图界定PLA2在生理和病理条件下的作用。
