title: Effect of 2-arachidonoylglycerol on myosin light chain phosphorylation and platelet activation: The role of phosphatidylinositol 3 kinase/AKT pathway.
abstract: The endocannabinoid 2-arachidonoylglycerol (2-AG) can be considered a true agonist as it is able to activate human platelets stimulating arachidonic acid release, thromboxane B2 formation and calcium intracellular elevation. Recently we have shown that 2-AG induces a rapid myosin light chain (MLC) phosphorylation/activation, early mediated by RhoA kinase (ROCK) signalling pathway and later by myosin light chain kinase. The aim of the present study was to investigate the role of phosphatidylinositol 3 kinase (PI3K)/AKT pathway in MLC phosphorylation and some downstream events such as actin polymerization, ATP secretion and aggregation. We demonstrated that PI3K in particular the isoforms α and β and AKT have a role in MLC phosphorylation. The stimulation of PI3K/AKT pathway activates ROCK. ROCK is directly involved in the early phase of MLC activation stimulating thr18 phosphorylation. MLC activation is strengthened through the MLC phosphatase inhibition, that is accomplished through the phosphorylation of MYPT1, catalytic subunit of MLC phosphatase, overall mediated by ROCK. In addition we have found that the PI3Kα/β isoforms and AKT are involved in the downstream mechanisms leading to actin polymerization, ATP secretion and aggregation of human platelets stimulated by 2-AG.
authors: Department of Pharmacy, Biochemistry Lab, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy.
authors: Maria Grazia
authors: MG
authors: Signorello
authors: Department of Pharmacy, Biochemistry Lab, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy. Electronic address: leoncini@unige.it.
authors: Giuliana
authors: G
authors: Leoncini
mesh_terms: D000199:Actins / Q000378:metabolism; D001095:Arachidonic Acids / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism; D058534:Class I Phosphatidylinositol 3-Kinases; D063388:Endocannabinoids / Q000008:administration & dosage*; D005989:Glycerides / Q000008:administration & dosage*; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D018994:Myosin Light Chains; C094503:glyceryl 2-arachidonate; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt; D054460:rho-Associated Kinases; D002118:Calcium
keywords: 2-Arachidonoylglycerol; Myosin light chain; Myosin light chain phosphatase; Phosphatidylinositol 3 kinase/AKT pathway; RhoA/RhoA kinase