Inhibition of phospholipase A2 reduces neurite outgrowth and neuronal viability
Inhibition of phospholipase A2 reduces neurite outgrowth and neuronal viability
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DOI：
10.1016/j.plefa.2006.10.002
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发表时间：
2007-01-01
影响因子：
3
通讯作者：
Gattaz, Wagner F.
中科院分区：
文献类型：
--
作者：
Forlenza, Orestes V.;Mendes, Camila T.;Gattaz, Wagner F.
磷脂酶A2（PLA（2））与神经发育过程和神经系统的早期发育有关。我们研究了抑制钙依赖性和钙非依赖性亚型的胞质PLA 2（cPLA 2和iPLA 2）对皮层和海马神经元原代培养物的发育和活力的影响。这些培养物中的PLA 2被甲基花生四烯酸-氟膦酸酯（MAFP）（cPLA 2和iPLA 2的不可逆抑制剂）或溴烯醇内酯（BEL）（不可逆选择性iPLA 2抑制剂）持续抑制。通过总细胞计数和形态学表征确定PLA 2抑制剂对神经元培养物发育的影响。用MTT测定定量神经元活力。PLA 2的抑制导致轴突发生和神经元活力的减少，破坏神经元稳态并导致神经元死亡。我们的结论是钙依赖性和钙非依赖性，胞浆PLA 2的功能完整性是必要的皮质和海马神经元的体外发育。(c)2006爱思唯尔有限公司版权所有。
Phospholipase A2 (PLA(2)) has been implicated in neurodevelopmental processes and in the early development of the nervous system. We investigated the effects of the inhibition of calcium-dependent and calcium-independent subtypes of cytosolic PLA2 (cPLA2 and iPLA2) on the development and viability of primary cultures of cortical and hippocampal neurons. PLA2 in these cultures was continuously inhibited with methylarachidonyl-fluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and iPLA2, or with bromoenol lactone (BEL), an irreversible selective iPLA2 inhibitor. The effect of PLA2 inhibitors on the development of neuronal cultures was ascertained by total cell count and morphological characterisation. Neuronal viability was quantified with MTT assays. Inhibition of PLA2 resulted in reduction of neuritogenesis and neuronal viability, disrupting neuronal homeostasis and leading to neuronal death. We conclude that the functional integrity of both calcium-dependent and calcium-independent, cytosolic PLA2 is necessary for the in vitro development of cortical and hippocampal neurons. (c) 2006 Elsevier Ltd. All rights reserved.