title: The effect of cyclosporine A on the phosphorylation of the AMPK pathway in the rat hippocampus.
abstract: Cyclosporine A (CsA), an immunosuppressant and calcineurin inhibitor, induces hyperlipidemia in humans and animals. AMP-activated protein kinase (AMPK) is involved in metabolic homeostasis and lipid metabolism through modulating downstream molecules acetyl CoA carboxylase (ACC) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR). AMPK activity is regulated by the phosphorylation at the Thr-172 residue by its upstream liver kinase B 1 (LKB1), Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ) or transforming growth-factor-β-activated kinase 1 (TAK1). AMPK can be deactivated through dephosphorylation by protein phosphatase 2Cα (PP2Cα). In this study, we demonstrated that phosphorylation at Thr-172-AMPK increased with a concurrent increase in the phosphorylation of Ser-431-LKB1 and Thr-184/187-TAK1 in the rat hippocampus at 5 h after an intraperitoneal CsA (50 mg/kg) injection. CsA did not affect the phosphorylation of Thr-196-Ca(2+)/calmodulin-dependent protein kinase 4 (CaMK4) and the amount of PP2Cα. An increased phosphorylation of Ser-79-ACC and Ser-872-HMG-CoAR was also observed. In conclusion, our data indicate that CsA activates the AMPK pathway in the rat hippocampus, which suggests that CsA affects the regulatory signaling pathway of lipid metabolism in the rat brain.
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hong Geun
authors.initials: HG
authors.lastname: Park
authors.forename: Heesun
authors.initials: H
authors.lastname: Yi
authors.forename: Se Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Yu
authors.forename: Yong Min
authors.initials: YM
authors.lastname: Ahn
authors.forename: Young Han
authors.initials: YH
authors.lastname: Lee
authors.forename: Myoung-Sun
authors.initials: MS
authors.lastname: Roh
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D016572:Cyclosporine; D004791:Enzyme Inhibitors; D020930:MAP Kinase Kinase Kinases; D017346:Protein Serine-Threonine Kinases; D000099151:MAP Kinase Kinase Kinase 7; C488755:Stk11 protein, rat