However, together PLA2 that acts on membrane phospholipids has been implicated in cell death and differentiation as well as intracellular membrane trafficking. In mammalian cells, PLA2 activity has been found to increase in response to numerous stimuli such as osmotic challenge, oxidative stress, ischemic conditions and expo sure to allergens. The synthesis of different cell specific sub types and activation of mammalian PLA2 are associ ated with cell injury and various pathophysiological con ditions. In the central nervous system, PLA2 is known to participate in many physiological activ ities and has been found to increase significantly fol lowing spinal cord injury. The role of PLA2 has also been documented in schizophrenia, brain trauma and Alzheimers disease besides global and focal ischemia in animal models.
Hippocampal slices sub jected to oxygen and glucose deprivation have been found to show Inhibitors,Modulators,Libraries an increase in PLA2 activity and a con comitant death of neuronal cells. Inhibition of cPLA2 has been found to result in an enhanced survival of the hip pocampal neurons. Evidently, cPLA2 knock out mice subjected to focal cerebral ischemia showed significant reduction in infarct volume and the extent of neurological impairment. Furthermore, Strokin et al demon strated that inhibition of iPLA2 during OGD could render neuroprotection to the hippocampal slice cultures. Fur thermore, simultaneous inhibition of cPLA2 and sPLA2 activities have also been shown to improve survival of glial cells subjected to ischemic injury. The snake venom PLA2 belongs Inhibitors,Modulators,Libraries to the Ca2 dependant secretory PLA2.
Venom phospholipases A2 possess an enzymic activity and a wide variety of pharmaco logical activities such as antiplatelet, anticoagulant, hemolytic, Inhibitors,Modulators,Libraries neurotoxic, myotoxic, Inhibitors,Modulators,Libraries edema inducing, hemorrhagic, cytolytic, cardiotoxic as well as an ability to bind antagonistically to muscarinic acetylcho line receptor. The snake venom phos pholipases are divided into two main groups, group I and group II, based on their primary structures. Inhibitors,Modulators,Libraries The group I PLA2 is found in abundance in the venom of cobras, kraits and sea snakes, while group II PLA2 is common in vipers and pit vipers. The cobra venom PLA2 belongs to group IA that is similar to the pancreatic type group IB protein but without the signature pancreatic loop struc ture. Venom of Naja sputatrtix, a Malayan spitting cobra, comprises of three isoforms of group 1A PLA2.
One of the neutral forms, nPLA 1 is a highly potent anticoagulant protein that exhibits rela tively high enzymic activity. This protein has also been shown to possess an ability to bind to all muscarinic receptor subtypes with a higher affinity to the m5 subtype. In this report, in contrast to the reported detrimental effects of mammalian phospholipase kinase inhibitor FTY720 A2 to the central nervous system, we demonstrate that neutral PLA2 from Naja sputatrix could reduce neuronal cell death and afford neuroprotection to rat brain subjected to transient focal ischemia.