Armugam Arunmozhiarasi, Cher Charmian D N, Lim KaiYing, Koh Dawn C I, Howells David W, Jeyaseelan Kandiah
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
BMC Neurosci. 2009 Sep 23;10:120. doi: 10.1186/1471-2202-10-120.
Phospholipase A2 liberates free fatty acids and lysophospholipids upon hydrolysis of phospholipids and these products are often associated with detrimental effects such as inflammation and cerebral ischemia. The neuroprotective effect of neutral phospholipase from snake venom has been investigated.
A neutral anticoagulant secretory phospholipase A2 (nPLA) from the venom of Naja sputatrix (Malayan spitting cobra) has been found to reduce infarct volume in rats subjected to focal transient cerebral ischemia and to alleviate the neuronal damage in organotypic hippocampal slices subjected to oxygen-glucose deprivation (OGD). Real-time PCR based gene expression analysis showed that anti-apoptotic and pro-survival genes have been up-regulated in both in vivo and in vitro models. Staurosporine or OGD mediated apoptotic cell death in astrocytoma cells has also been found to be reduced by nPLA with a corresponding reduction in caspase 3 activity.
We have found that a secretory phospholipase (nPLA) purified from snake venom could reduce infarct volume in rodent stroke model. nPLA, has also been found to reduce neuronal cell death, apoptosis and promote cell survival in vitro ischemic conditions. In all conditions, the protective effects could be seen at sub-lethal concentrations of the protein.
磷脂酶A2在磷脂水解时释放游离脂肪酸和溶血磷脂，这些产物常与炎症和脑缺血等有害作用相关。已对蛇毒中性磷脂酶的神经保护作用进行了研究。
已发现来自马来喷毒眼镜蛇毒液的一种中性抗凝分泌型磷脂酶A2（nPLA）可减少局灶性短暂性脑缺血大鼠的梗死体积，并减轻氧糖剥夺（OGD）处理的器官型海马切片中的神经元损伤。基于实时PCR的基因表达分析表明，抗凋亡和促生存基因在体内和体外模型中均上调。还发现nPLA可减少星形细胞瘤细胞中星形孢菌素或OGD介导的凋亡细胞死亡，同时半胱天冬酶3活性相应降低。
我们发现从蛇毒中纯化的一种分泌型磷脂酶（nPLA）可减少啮齿动物中风模型中的梗死体积。还发现nPLA在体外缺血条件下可减少神经元细胞死亡、凋亡并促进细胞存活。在所有情况下，在该蛋白的亚致死浓度下均可观察到保护作用。
