Docosahexaenoic acid decreases phospholipase A2 activity in the neurites/nerve growth cones of PC12 cells.
Docosahexaenoic acid (DHA) accumulates in nerve growth cones (NGC) during perinatal development and it is neuroprotective in ischemia. Because the phospholipases A2 (PLA2) are present in NGC and these enzymes function in both ischemia and long-term potentiation, the relationship between DHA and PLA2 was investigated in the NGC of nerve growth factor-differentiated PC12 cells. When PC12 cells were incubated with [3H]DHA, it primarily esterified in ethanolamine glycerolipids and concentrated initially in cell bodies with similar levels present in the neurite/nerve growth cone (N/NGC) fraction after 4 days. PLA2 activity in the N/NGC fraction was investigated using [14C]arachidonic acid-labeled phosphatidylinositol ([14C-AA]PI) as substrate. Heat denaturation and pharmacological inhibition showed that much of the PLA2 activity was calcium-independent and secretory rather than cytosolic. Supplementing the media with as little as 33 nM DHA significantly reduced PLA2 activity in the N/NGC fraction.
Martin
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University of Oklahoma College of Medicine, Department of Cell Biology and Oklahoma Center for Neuroscience, Oklahoma City 73104, USA. rex-martin@ouhsc.edu
D000818:Animals; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D004983:Ethanolamines; D020439:Growth Cones / Q000187:drug effects* / Q000201:enzymology; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology; D016716:PC12 Cells; D010741:Phospholipases A / Q000187:drug effects* / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats
D004983:Ethanolamines; D004281:Docosahexaenoic Acids; D010741:Phospholipases A; D054467:Phospholipases A2