Group III secreted phospholipase A2 causes apoptosis in rat primary cortical neuronal cultures.
Secreted phospholipase A(2) (sPLA(2)) has been shown to cause both necrotic and apoptotic neuronal injury in the central nervous system. The acute effects of group III sPLA(2) (sPLA(2)-III) include an ability to potentiate glutamate-induced necrosis and calcium influx in primary rat neuronal cultures. Thus, a brief exposure to glutamate and sPLA(2)-III results in an immediate potentiated calcium influx and a potentiated necrosis the following day after treatment, compared to addition of either agonist alone. In contrast to these acute effects, sPLA(2) from both groups IB and IIA have been shown to induce neuronal cell death via apoptosis. Here, we offer the first evidence that group III sPLA(2) potently causes extensive neuronal apoptosis in rat cortical cultures, as evidenced by DNA fragmentation. Distinct from this effect, even high concentrations of glutamate did not cause neuronal damage under the same conditions, and there was no evidence of sPLA(2) damage to cortical astrocytes.
D000818:Animals; D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology* / Q000648:ultrastructure; D053938:DNA Fragmentation; D018698:Glutamic Acid / Q000009:adverse effects / Q000378:metabolism; D054520:Group III Phospholipases A2; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology* / Q000648:ultrastructure; D010741:Phospholipases A / Q000009:adverse effects* / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley
D016718:Arachidonic Acid; D018698:Glutamic Acid; D010741:Phospholipases A; D054520:Group III Phospholipases A2; D054467:Phospholipases A2; C083622:Pla2g3 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases