Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 35, Issue 8, Pages 1933-1937Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2011.09.008
Keywords
AMP-activated protein kinase; Cyclosporine A; Lipid metabolism; Phosphorylation; Rat brain
Funding
- Ministry for Health, Welfare & Family Affairs, Republic of Korea [A084888]
- Korea Health Promotion Institute [A084888] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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), Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKK beta) or transforming growth-factor-beta-activated kinase 1 (TAK1). AMPK can be deactivated through dephosphorylation by protein phosphatase 2C alpha (PP2C alpha). 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-Ca2+/calmodulin-dependent protein kinase 4 (CaMK4) and the amount of PP2C alpha. 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. (C) 2011 Elsevier Inc. All rights reserved.
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