NDLI: Rho-kinase regulates human platelet activation induced by thromboxane A2 independently of p38 MAP kinase.

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Rho-kinase regulates human platelet activation induced by thromboxane A2 independently of p38 MAP kinase.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Iida, Yuko Doi, Tomoaki Tokuda, Haruhiko Matsushima-Nishiwaki, Rie Tsujimoto, Masanori Kuroyanagi, Gen Yamamoto, Naohiro Enomoto, Yukiko Tanabe, Kumiko Otsuka, Takanobu Iwama, Toru Ogura, Shinji Kozawa, Osamu Iida, Hiroki
Description	Country affiliation: Japan Author Affiliation: Iida Y ( Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan); Doi T ( Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.); Tokuda H ( Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan); Matsushima-Nishiwaki R ( Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.); Tsujimoto M ( Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.); Kuroyanagi G ( Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan); Yamamoto N ( Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan); Enomoto Y ( Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.); Tanabe K ( Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.); Otsuka T ( Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8603, Japan.); Iwama T ( Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.); Ogura S ( Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.); Kozawa O ( Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan. Electronic address: okozawa@gifu-u.ac.jp.); Iida H ( Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.)
Abstract	We have previously demonstrated that ristocetin, an activator of GPIb/IX/V, induces the release of soluble CD40 ligand (sCD40L) via thromboxane A2 production in human platelets. It has been shown that thromboxane A2 induces the activation of Rho-kinase, a downstream effector of Rho, in human platelets. In the present study, we investigated the exact roles of Rho-kinase in thromboxane A2-induced platelet activation. We found that U46619, a thromboxane receptor (TP) agonist, induced the phosphorylation of cofilin, a target of Rho-kinase signaling, and that the cofilin phosphorylation by U46619 was suppressed by Y27632 or fasudil, specific inhibitors of Rho-kinase. Y27632 and fasudil markedly decreased large platelet aggregate formation by U46619. The release of sCD40L and secretion of platelet-derived growth factor (PDGF)-AB stimulated by U46619 were inhibited by Y27632 and fasudil. SB203580, a specific inhibitor of p38 mitogen-activated protein (MAP) kinase, reduced the sCD40L release and PDGF-AB secretion. Y27632 and fasudil failed to affect the phosphorylation of p38 MAP kinase whereas SB203580 had little effect on the phosphorylation of cofilin induced by U46619. In conclusion, our results strongly suggest that Rho-kinase regulates thromboxane A2-induced human platelet activation independently of p38 MAP kinase.
File Format	HTM / HTML
ISSN	09523278
Volume Number	94
e-ISSN	15322823
Journal	Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA)
Language	English
Publisher	Elsevier
Publisher Date	2015-03-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Endocrinology Platelet Activation Drug Effects Signal Transduction Thromboxane A2 Pharmacology P38 Mitogen-activated Protein Kinases Metabolism Rho-associated Kinases 15-hydroxy-11 Alpha,9 Alpha-(epoxymethano)prosta-5,13-dienoic Acid Actin Depolymerizing Factors Amides Blood Platelets Enzyme Inhibitors Humans Imidazoles Phosphorylation Pyridines Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Clinical Biochemistry

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Involvement of Rac in thromboxane A2induced human platelet activation: regulation of sCD40 ligand release and PDGFAB secretion.

B-crystallin reduces ristocetininduced soluble CD40 ligand release in human platelets: suppression of thromboxane A2 generation.

Effect of antithrombin III on glycoprotein Ib/IX/V activation in human platelets: suppression of thromboxane A2 generation.

Regulation of thromboxane receptor activation in human platelets.

Rho-kinase inhibitor inhibits both myosin phosphorylation-dependent and -independent enhancement of myofilament $Ca^{2+}$ sensitivity in the bovine middle cerebral artery

Binding kinetics and antiplatelet activities of picotamide, a thromboxane A2 receptor antagonist.

Mechanism of platelet inhibition by nitric oxide: in vivo phosphorylation of thromboxane receptor by cyclic GMP-dependent protein kinase.

Activation of $G_{12}/G_{13}$ Results in Shape Change and Rho/Rho-Kinase–mediated Myosin Light Chain Phosphorylation in Mouse Platelets

Heterogeneity of thromboxane A2 (TP-) receptors: evidence from antagonist but not agonist potency measurements.

Rho-kinase regulates human platelet activation induced by thromboxane A2 independently of p38 MAP kinase.

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