The effect of cyclosporine A on the phosphorylation of the AMPK pathway in the rat hippocampus

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 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 5h after an intraperitoneal CsA (50mg/kg) injection. CsA did not affect the phosphorylation of Thr-196-Ca2+/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. ► Cyclosporine A (CsA), an calcineurin inhibitor, induces hyperlipidemia. ► AMP-activated protein kinase (AMPK) is involved in lipid metabolism. ► The activity of AMPK pathway in the rat hippocampus was examined after CsA treatment. ► CsA increased the phosphorylations of AMPK, upstream and downstream molecules. ► CsA affects the lipid metabolism in the rat brain through regulation of AMPK pathway.