Docosahexaenoic acid decreases phospholipase A2 activity in the neurites/nerve growth conesof PC12 cells

Abstract

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.

Essential fatty acids and the brain: possible health implications

“…Thus, limiting the amount membrane AA, through manipulation by dietary n-6 FAs such as DHA or EPA will inevitably reduce the amount of free AA generated during ischemia/reperfusion and consequently less AA metabolites. In addition, it was reported earlier, that the activity of PLA 2 , a rate limiting step in the release of AA from membrane phospholipid could be reduced by dietary DHA, which too can reduce the availability of free AA for metabolism into various eicosanoids [59,80].…”

“…This important ®nding raised many questions, but in particular the issue about the biochemical and biophysical mechanisms that lead to their essentiality. To date, a multitude of mechanisms have been explored, for example, their eects on; the structural integrity and¯uidity of membranes [33,130]; enzyme activities [80,120,125]; lipid-protein interactions [117]; and their role as precursors for eicosanoids, such as prostaglandins, leukotrienes and thromboxanes.…”

Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus

“…Various mechanisms have been suggested to account for these physiological changes in the brain and retina, as reviewed recently by Kurlack and Stephenson (10), Lauritzen et al (11), and Salem et al (12). Briefly, DHA plays a crucial role in membrane order (membrane fluidity), which can influence the function of membrane receptors such as rhodopsin (13,14); regulation of membrane-bound enzymes (Na͞K-dependent ATPase) (15); dopaminergic and serotoninergic neurotransmission (16); signal transduction via effects on inositol phosphates, diacylglycerol, and protein kinase C (17); regulation of the synthesis of eicosanoids derived from arachidonic acid (AA) (10); regulation of gene expression (18)(19)(20); regulation of phosphatidylserine levels (21); protection of neural cells from apoptotic death (22,25); stimulation of neurite outgrowth in PC12 cells (23,24); selective accumulation of DHA by synaptic growth cones during neuronal development (23,24); regulation of nerve growth factor (29); and regulation of neuron size (26,27).…”

Phospholipase A2 and Signaling Pathways in Pheochromocytoma PC12 Cells

“…For example, similarly to PLA2 docosahexaenoic acid (22:6 n-3) is present in neurite growth cones. This acid decreases time-course activity of cytosolic PLA2 (Martin, 1998) and attenuates (Kim et al, 2001) or accelerates (Schonfeld et al, 2007) apoptotic death in PC12 cells. On the other hand arachidonic acid suppresses neurite outgrowth induced by nerve growth factor (Ikemoto et al, 1997) and also may be both anti-apoptotic (Kim et al, 2001) and pro-apoptotic at deprivation of NGF and serum (Atsumi et al, 1997) in PC12 (see also section 4).…”

“…The effects of these enzymes will not be considered in details in the present paper. At the same time, increased activity of endogenous PLA2 has been found in nerve growth cones in differentiating PC12 and much of this PLA2 activity has been shown to be calciumindependent and secretory rather than cytosolic (Martin, 1998) or solely secretory (Ferrini et al, 2010). One cannot assert, however, that the activation of endogenous PLA2 is indeed an initial cause of neuritogenesis.…”