title: The effect of systemic injection of cyclosporin A on the phosphorylation of the PKC substrates MARCKS and GAP43 in the rat hippocampus.
abstract: Cyclosporin A (CsA) is an inhibitor of calcineurin, a calcium/calmodulin dependent serine/threonine phosphatase. Protein kinase C (PKC) is a family of serine/threonine kinases. Both calcineurin and PKC are implicated in psychiatric diseases and the therapeutic mechanisms of treatment agents. It has been reported that calcineurin interacts with components of PKC signaling pathways. We administrated 50mg/kg CsA into rats by intraperitoneal injection and examined the acute effect of single systemic CsA on the locomotor activity of rats and the phosphorylation of PKC and its substrates GAP43 and MARCKS. Systemic CsA increased locomotor activity beginning 1h after injection. The immunoreactivity of p-MARCKS(S152/156) was higher in the CsA group 1h after injection, whereas p-GAP43(S41) immunoreactivity was increased by CsA after 5h. The immunoreactivity of p-PKC pan was increased by CsA at both 1 and 5h after administration. Our data suggest that activation of the PKC pathway might be related to CsA-induced hyperlocomotion.
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.
authors.forename: Heesun
authors.initials: H
authors.lastname: Yi
authors.forename: Se Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Hong Geun
authors.initials: HG
authors.lastname: Park
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Yu
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D019922:GAP-43 Protein / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D019922:GAP-43 Protein; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; C000619712:Marcks protein, rat; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D016572:Cyclosporine; D011493:Protein Kinase C; D019703:Calcineurin