Rac2 GTPase activation by angiotensin II is modulated by Ca2C/calcineurin and mitogen-activated protein kinases in human neutrophils
Data(s) |
13/03/2012
13/03/2012
01/11/2007
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Resumo |
Angiotensin II (Ang II) highly stimulates superoxide anion production by neutrophils. The G-protein Rac2 modulates the activity of NADPH oxidase in response to various stimuli. Here, we describe that Ang II induced both Rac2 translocation from the cytosol to the plasma membrane and Rac2 GTP-binding activity. Furthermore, Clostridium difficile toxin A, an inhibitor of the Rho-GTPases family Rho, Rac and Cdc42, prevented Ang II-elicited O2-/ROS production, phosphorylation of the mitogen-activated protein kinases (MAPKs) p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2, and Rac2 activation. Rac2 GTPase inhibition by C. difficile toxin A was accompanied by a robust reduction of the cytosolic Ca(2)(+) elevation induced by Ang II in human neutrophils. Furthermore, SB203580 and PD098059 act as inhibitors of p38MAPK and ERK1/2 respectively, wortmannin, an inhibitor of phosphatidylinositol-3-kinase, and cyclosporin A, a calcineurin inhibitor, hindered both translocation of Rac2 from the cytosol to the plasma membrane and enhancement of Rac2 GTP-binding elicited by Ang II. These results provide evidence that the activation of Rac2 by Ang II is exerted through multiple signalling pathways, involving Ca(2)(+)/calcineurin and protein kinases, the elucidation of which should be insightful in the design of new therapies aimed at reversing the inflammation of vessel walls found in a number of cardiovascular diseases. This work was financed by grants from the Ministerio de Educación y Ciencia (BFU2006-13802), and the Consejería de Innovación, Ciencia y Empresa (P06-CTS-1936), Junta de Andalucía, Spain, awarded to F S. |
Identificador |
El Bekay R, Alba G, Reyes ME, Chacón P, Vega A, Martín-Nieto J, et al. Rac2 GTPase activation by angiotensin II is modulated by Ca2C/calcineurin and mitogen-activated protein kinases in human neutrophils. J Mol Endocrinol. 2007 Nov;39(5):351-63. 0952-5041 http://hdl.handle.net/10668/355 17975262 10.1677/JME-07-0074 |
Idioma(s) |
en |
Publicador |
European Society of Endocrinology |
Relação |
Journal of Molecular Endocrinology http://jme.endocrinology-journals.org/content/39/5/351 |
Direitos |
Acceso abierto |
Palavras-Chave | #protein kinases #inflammation #Angiotensina #proteínas quinasas #inflamación #enfermedad cardiovascular #Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Angiotensins::Angiotensin II #Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Calcineurin #Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Calcium Metabolism Disorders #Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Biological Transport::Cell Membrane Permeability #Medical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Macrocyclic Compounds::Peptides, Cyclic::Cyclosporins::Cyclosporine #Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Enzyme Activation #Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors::Angiotensin-Converting Enzyme Inhibitors #Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Mitogen-Activated Protein Kinases #Medical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Granulocytes::Neutrophils #Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Phosphatidylinositol 3-Kinases #Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Oxygen Compounds::Reactive Oxygen Species #Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction #Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::GTP Phosphohydrolases::GTP-Binding Proteins::Monomeric GTP-Binding Proteins::rho GTP-Binding Proteins::rac GTP-Binding Proteins #Medical Subject Headings::Diseases::Cardiovascular Diseases |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/published Artículo |