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Open Access Highly Accessed Research article

A secretory phospholipase A2-mediated neuroprotection and anti-apoptosis

Arunmozhiarasi Armugam1, Charmian DN Cher1, KaiYing Lim1, Dawn CI Koh1, David W Howells2 and Kandiah Jeyaseelan1*

Author Affiliations

1 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597, Singapore

2 National Stroke Research Institute, Austin Health, Studley Rd, Heidelberg, Victoria 3084, Australia

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BMC Neuroscience 2009, 10:120  doi:10.1186/1471-2202-10-120

Published: 23 September 2009

Abstract

Background

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.

Results

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.

Conclusion

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.