Roles of phospholipases A(2) in brain cell and tissue injury associated with ischemia and excitotoxicity
Roles of phospholipases A(2) in brain cell and tissue injury associated with ischemia and excitotoxicity
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DOI：
10.1016/0929-7855(96)00503-2
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发表时间：
1996-09-01
期刊：
影响因子：
--
通讯作者：
Bonventre, JV
中科院分区：
文献类型：
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作者：
Bonventre, JV
磷脂酶A（2）（PLA（2））活性是中枢神经系统中破坏性细胞过程的重要贡献者。在沙鼠脑和大鼠脑的神经元培养物中，已鉴定出两种胞质形式的钙非依赖性PLA（2）。皮层神经元培养物的无细胞提取物中的PLA（2）酶活性在细胞暴露于谷氨酸后上调。短暂暴露于钙离子载体或佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）可稳定增强PLA（2）活性。PLA（2）的两种胞质形式的稳定活化发生在细胞死亡的证据之前，并且这种活化是可逆的。较大分子量形式表征为cPLA（2）。较小的形式（类似于14 kDa）与第I组和第II组PLA不同（2）。暴露于谷氨酸使较小形式的钙激活曲线向左移动，表明PLA的新调节机制（2）。谷氨酸诱导的PLA（2）活性的稳定增强，通过涉及钙和蛋白激酶C激活的过程，是一个潜在的分子开关，可能介导突触功能的变化和兴奋性毒性的贡献。
Phospholipase A(2) (PLA(2)) activity is an important contributor to destructive cellular processes in the central nervous system. Two cytosolic forms of calcium independent PLA(2) have been characterized in the gerbil brain and the neuronal cultures from rat brain. PLA(2) enzymatic activity in cell free extracts from cortical neuronal cultures is upregulated after cells are exposed to glutamate. Brief exposure to a calcium ionophore or phorbol 12-myristate 13-acetate (PMA) stably enhanced PLA(2) activity. Stable activation of the two cytosolic forms of PLA(2) occur prior to evidence of cell death and this activation is reversible. The larger molecular mass form was characterized as cPLA(2). The smaller form (similar to 14 kDa) was distinct from Group I and II PLA(2). Exposure to glutamate shifted the calcium activation curve of the smaller form to the left suggesting a novel mechanism of regulation of PLA(2). Glutamate-induced stable enhancement of PLA(2) activity, by processes involving calcium and protein kinase C activation, is a potential molecular switch likely mediating changes in synaptic function and contribution to excitotoxicity.