A secretory phospholipase A2-mediated neuroprotection and anti-apoptosis.
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.


CONCLUSIONS
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.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. bchaa@nus.edu.sg
Arunmozhiarasi
A
Armugam
Charmian D N
CD
Cher
KaiYing
K
Lim
Dawn C I
DC
Koh
David W
DW
Howells
Kandiah
K
Jeyaseelan
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004546:Elapid Venoms / Q000737:chemistry; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009924:Organ Culture Techniques; D054467:Phospholipases A2 / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004546:Elapid Venoms; D018696:Neuroprotective Agents; D054467:Phospholipases A2; D010959:Tissue Plasminogen Activator; D005947:Glucose