Platelet-activating factor-induced synaptic facilitation is associated with increased calcium/calmodulin-dependent protein kinase II, protein kinase C and extracellular signal-regulated kinase activities in the rat hippocampal CA1 region.
Platelet-activating factor (PAF) is an important inflammatory lipid mediator affecting neural plasticity. In the present study, we demonstrated how PAF affects synaptic efficacy through activation of protein kinases in the rat hippocampal CA1 region. In cultured hippocampal neurons, 10 to 1000 nM PAF stimulated autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of synapsin I and myristoylated alanine-rich protein kinase C substrate (MARCKS). In hippocampal CA1 slices, field excitatory postsynaptic potentials (fEPSPs) induced by stimulation of the Schaffer collateral/commissural pathways were significantly increased 10-50 min after exposure to 100 to 1000 nM PAF. Immunoblotting analysis showed that 100 nM PAF treatment for 10 or 50 min significantly and persistently increased CaMKII autophosphorylation in the hippocampal CA1 region. Increased protein kinase Calpha (PKCalpha) autophosphorylation was also seen at the same time point after PAF exposure. By contrast, extracellular signal-regulated kinase (ERK) phosphorylation was slightly but significantly increased at 10 min after PAF exposure. Consistent with increased CaMKII autophosphorylation, AMPA-type glutamate receptor subunit 1 (GluR1) (Ser-831) phosphorylation as a CaMKII postsynaptic substrate significantly increased after 10 or 50 min of treatment, whereas synapsin I (Ser-603) phosphorylation as a presynaptic substrate increased at 10 min in the hippocampal CA1 region. Phosphorylation of MARCKS (Ser-152/156) and NMDA receptor subunit 1 (NR1) (Ser-896) as PKCalpha substrates also significantly increased after 10 min but had not further increased by 50 min in the CA1 region. Increased of fEPSPs induced by PAF treatment completely and/or partly inhibited by KN93 and/or U0126 treatment. These results suggest that PAF induces synaptic facilitation through activation of CaMKII, PKC and ERK in the hippocampal CA1 region.
Moriguchi
S
S
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan. shigeki@mail.pharm.tohoku.ac.jp
Shioda
N
N
Yamamoto
Y
Y
Fukunaga
K
K
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000201:enzymology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation / Q000187:drug effects; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D051571:Protein Kinase C-alpha / Q000187:drug effects / Q000378:metabolism*; D021122:Protein Subunits / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D016704:Synapsins / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D047908:Intracellular Signaling Peptides and Proteins; C000619712:Marcks protein, rat; D008565:Membrane Proteins; D010972:Platelet Activating Factor; D021122:Protein Subunits; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016704:Synapsins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D051571:Protein Kinase C-alpha; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases