Canna~Fangled Abstracts

Activation of CaMKKβ/AMPKα pathway by 2-AG in human platelets.

By June 29, 2017No Comments
J Cell Biochem. 2017 Jun 29. doi: 10.1002/jcb.26251.
[Epub ahead of print]

Abstract

pm-2-site-207The objective of this study was to determine whether AMPK is activated by 2-arachidonoylglycerol (2-AG) and participates to the cytoskeleton control in human platelets. We found that 2-AG stimulates the AMPKα activation through a Ca2+ /Calmodulin-dependent pathway as the specific inhibition of the CaMKKβ by STO-609 inhibits the AMPKα phosphorylation/activation. Moreover the CaMKKβ/AMPKα pathway activated by 2-AG is involved in the phosphorylation of cofilin, vasodilator stimulated phosphoprotein (VASP) and myosin light chain (MLCs). These proteins participate to actin cytoskeletal remodelling during aggregation. We found that the phosphorylation/activation inhibition of these proteins is associated with a significant reduction in actin polymerization, aggregation, ATP and α-granule secretion. Finally AMPKα activation, Cofilin, VASP and MLCs phosphorylation are significantly reduced by SR141716, the specific inhibitor of type 1 cannabinoid (CB1) receptor, suggesting that the CB1 receptor is involved in the 2-AG effect. In conclusion we have shown that the CaMKKβ/AMPKα pathway is activated by 2-AG in human platelets and controls the phosphorylation of key proteins involved in actin polymerization and aggregation. This article is protected by copyright. All rights reserved.

KEYWORDS:

Aggregation; CaMKKβ/AMPK pathway; arachidonoylglycerol; cytoskeleton reorganization; human platelets; signal transduction

PMID: 28661046

 

DOI: 10.1002/jcb.26251
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