Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/355
Título : Rac2 GTPase activation by angiotensin II is modulated by Ca2C/calcineurin and mitogen-activated protein kinases in human neutrophils
Autor : El Bekay, Rajaa
Alba, Gonzalo
Reyes, M Edith
Chacón, Pedro
Vega, Antonio
Martín-Nieto, José
Jiménez, Juan
Ramos, Eladio
Oliván, Josefina
Pintado, Elizabeth
Sobrino, Francisco
Filiación: [El Bekay,R; Alba,G; Reyes,ME; Chacón,P; Vega,A; Pintado,E; Sobrino,F] Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla. [Martín-Nieto,J] Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Alicante, Spain.[Ramos,E; Oliván,J] Unidad de Hipertensión, Hospital Universitario Virgen Macarena, Sevilla, Spain
Palabras clave : protein kinases
inflammation
Angiotensina
proteínas quinasas
inflamación
enfermedad cardiovascular
MeSH: 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
Fecha de publicación : Nov-2007
Editorial : European Society of Endocrinology
Cita Bibliográfica: 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.
Abstract: 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.
URI: http://hdl.handle.net/10668/355
Versión del editor : http://jme.endocrinology-journals.org/content/39/5/351
DOI: 10.1677/JME-07-0074
ISSN : 0952-5041
Appears in Collections:01- Artículos - Hospital Virgen Macarena

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