Enhancement of long-term potentiation by cis-unsaturated fatty acid: relation to protein kinase C and phospholipase A2
Open Access
- 1 November 1987
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 7 (11) , 3783-3792
- https://doi.org/10.1523/jneurosci.07-11-03783.1987
Abstract
Previous correlative and interventive work from this laboratory has suggested that activation of protein kinase C (PKC) is important for the maintenance of the hippocampal long-term potentiation (LTP) response. One such study demonstrated that application of the cis- unsaturated fatty acid, oleate, a newly discovered PKC activator, could prolong the time course of LTP. The present study explored the mechanism of cis-unsaturated fatty acid action on LTP produced by perforant path stimulation. First, neither oleate application nor high- frequency stimulation alone produced a persistent change in synaptic transmission, while the 2 in conjunction did so. This suggests that oleate acts synergistically with the consequences of this stimulation to produce an enhancement of the LTP response. Second, oleate enhancement of LTP was more potent when applied in the perforant path synaptic terminal zone than in the dentate hilus, implying that the site of oleate action is at the synapse (where PKC is reported to be enriched). Third, translocation of PKC activity to the membrane was significantly increased after oleate-enhanced LTP relative to vehicle controls. PKC translocation was found to be unaltered by oleate application alone. Fourth, mepacrine blockade of the Ca2+-dependent enzyme phospholipase A2, which releases endogenous oleate from membrane phospholipids, inhibited the time-course of a persistent LTP response. This inhibition was shown to be reversible with oleate application. We propose that high-frequency stimulation produces an elevation of intracellular Ca2+, which then triggers phospholipase A2-mediated oleate release. This free oleate then could act in synergy with processes that render PKC oleate-sensitive to produce a persistent activation of PKC, which is critical for and leads to the persistence of the LTP response.This publication has 27 references indexed in Scilit:
- Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.Published by Elsevier ,2021
- Calcium-activated, phospholipid-dependent protein kinase from rat brain. Subcellular distribution, purification, and properties.Journal of Biological Chemistry, 1982
- Long‐term synaptic enhancement and short‐term potentiation in rat fascia dentata act through different mechanismsThe Journal of Physiology, 1982
- Mepacrine blocks beta-adrenergic agonist-induced desensitization in astrocytoma cells.Proceedings of the National Academy of Sciences, 1980
- Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids.Journal of Biological Chemistry, 1979
- Adenylate cyclase activation by the .beta.-adrenergic receptors as a diffusion-controlled processBiochemistry, 1979
- Fatty acid stimulation of membrane phosphatidylinositol hydrolysis by brain phosphatidylinositol phosphodiesteraseBiochemical Journal, 1979
- Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. I. Purification and characterization of an active enzyme from bovine cerebellum.Journal of Biological Chemistry, 1977
- Entorhinal Activation of Dentate Granule CellsActa Physiologica Scandinavica, 1966
- PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENTJournal of Biological Chemistry, 1951