The effect of systemic injection of cyclosporin A on the phosphorylation of the PKC substrates MARCKS and GAP43 in the rat hippocampus |
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Authors: | Heesun Yi Se Hyun Kim Hong Geun Park Hyun Sook Yu Yong Sik Kim |
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Institution: | 1. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea;2. Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea;3. Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Republic of Korea;4. Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea |
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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 50 mg/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 1 h after injection. The immunoreactivity of p-MARCKS(S152/156) was higher in the CsA group 1 h after injection, whereas p-GAP43(S41) immunoreactivity was increased by CsA after 5 h. The immunoreactivity of p-PKC pan was increased by CsA at both 1 and 5 h after administration. Our data suggest that activation of the PKC pathway might be related to CsA-induced hyperlocomotion. |
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Keywords: | Calcineurin Protein kinase C Growth-associated protein43 Myristoylated alanine-rich C kinase substrate Hyperlocomotion |
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