Forlenza Orestes V, Mendes Camila T, Marie Suely K N, Gattaz Wagner F
Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, Rua Dr. Ovídio Pires de Campos s/n, 05403-010 Sao Paulo, Brazil.
Prostaglandins Leukot Essent Fatty Acids. 2007 Jan;76(1):47-55. doi: 10.1016/j.plefa.2006.10.002. Epub 2006 Dec 21.
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.
磷脂酶A2（PLA(2)）与神经发育过程以及神经系统的早期发育有关。我们研究了抑制胞质磷脂酶A2（cPLA2和iPLA2）的钙依赖性和非钙依赖性亚型对皮质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PLA2用甲基花生四烯酰氟磷酸酯（MAFP，一种cPLA2和iPLA2的不可逆抑制剂）或溴烯醇内酯（BEL，一种不可逆的选择性iPLA2抑制剂）持续抑制。通过细胞总数和形态学特征确定PLA2抑制剂对神经元培养物发育的影响。用MTT法对神经元活力进行定量。PLA2的抑制导致神经突生长和神经元活力降低，破坏神经元内环境稳定并导致神经元死亡。我们得出结论，钙依赖性和非钙依赖性胞质磷脂酶A2的功能完整性对于皮质和海马神经元的体外发育是必要的。
