TAILIEUCHUNG - Báo cáo Y học: Convulxin induces platelet shape change through myosin light chain kinase and Rho kinase

Once platelets are activated, the first event tooccur is a rapid change in shape, associated with Ca 2+ /calmodulin-dependent myosin light chain (MLC) phosphorylation and withRhokinase activation. The purpose of this studywas to investigate which is the biochemical pathway that leads to platelet shape change in response to convulxin, a selective GpVI activator, and to verify whether MLC phosphoryla-tion is essential for this process. | Eur. J. Biochem. 269 5878-5884 2002 FEBS 2002 doi Convulxin induces platelet shape change through myosin light chain kinase and Rho kinase Silvia Riondino Pier P. Gazzaniga and Fabio M. Pulcinelli Department of Experimental Medicine and Pathology Universita La Sapienza Rome Italy Once platelets are activated the first event to occur is a rapid change in shape associated with Ca2 calmodulin-dependent myosin light chain MLC phosphorylation and with Rho kinase activation. The purpose of this study was to investigate which is the biochemical pathway that leads to platelet shape change in response to convulxin a selective GpVI activator and to verify whether MLC phosphorylation is essential for this process. The inhibition of the Ca2 -dependent pathway by means of the Ca2 chelator BAPTA the Ca2 calmodulin inhibitor W-7 or the cAMP enhancing drug iloprost reduced about 50 of platelet shape change in response to convulxin. The treatment with either the Rho kinase inhibitors Y27632 or HA 1077 had no effect on platelet shape change induced by convulxin. When both Ca2 calmodulin-dependent and Rho kinase-dependent pathways were concomitantly inhibited by the combined use of Y27632 plus BAPTA W-7 or iloprost platelet shape change was completely abolished. Our findings suggest that convulxin-induced platelet shape change occurs via both pathways the Ca2 calmodulin-dependent which appears to be more important and the Rho kinase-dependent one. The pattern of MLC phosphorylation was not modified by Rho kinase inhibitors. Conversely the inhibition of the Ca2 -dependent pathway caused a strong reduction of MLC phosphorylation in BAPTA-treated platelets and a total inhibition in W-7 or iloprost-treated platelets. Our results demonstrate that following Rho kinase-dependent pathway platelet shape change can occur without the involvement of MLC phosphorylation. Keywords convulxin cyclic AMP myosin light chain kinase platelet shape change Rho kinase. One

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