RT Journal Article
T1 Rac2 GTPase activation by angiotensin II is modulated by Ca2C/calcineurin and mitogen-activated protein kinases in human neutrophils
A1 El Bekay, Rajaa
A1 Alba, Gonzalo
A1 Reyes, M Edith
A1 Chacón, Pedro
A1 Vega, Antonio
A1 Martín-Nieto, José
A1 Jiménez, Juan
A1 Ramos, Eladio
A1 Oliván, Josefina
A1 Pintado, Elizabeth
A1 Sobrino, Francisco
K1 protein kinases
K1 inflammation
K1 Angiotensina
K1 proteínas quinasas
K1 inflamación
K1 enfermedad cardiovascular
AB 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.
PB European Society of Endocrinology
SN 0952-5041
YR 2007
FD 2007-11
LK http://hdl.handle.net/10668/355
UL http://hdl.handle.net/10668/355
LA en
NO 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.
DS RISalud
RD Apr 4, 2025