Angiotensin II binding to angiotensin I-converting enzyme triggers calcium signaling

Item Type:	Article
Title:	Angiotensin II binding to angiotensin I-converting enzyme triggers calcium signaling
Creators Name:	Guimaraes, P.B. and Alvarenga, E.C. and Siqueira, P.D. and Paredes-Gamero, E.J. and Sabatini, R.A. and Morais, R.L. and Reis, R.I. and Santos, E.L. and Teixeira, L.G. and Casarini, D.E. and Martin, R.P. and Shimuta, S.I. and Carmona, A.K. and Nakaie, C.R. and Jasiulionis, M.G. and Ferreira, A.T. and Pesquero, J.L. and Oliveira, S.M. and Bader, M. and Costa-Neto, C.M. and Pesquero, J.B.
Abstract:	Angiotensin (Ang) I-converting enzyme (ACE) is involved in the control of blood pressure by catalyzing the conversion of Ang I into the vasoconstrictor Ang II and degrading the vasodilator peptide bradykinin. Human ACE also functions as a signal transduction molecule, and the binding of ACE substrates or its inhibitors initiates a series of events. In this study, we examined whether Ang II could bind to ACE generating calcium signaling. Chinese hamster ovary cells transfected with an ACE expression vector reveal that Ang II is able to bind with high affinity to ACE in the absence of the Ang II type 1 and type 2 receptors and to activate intracellular signaling pathways, such as inositol 1,4,5-trisphosphate and calcium. These effects could be blocked by the ACE inhibitor, lisinopril. Calcium mobilization was specific for Ang II, because other ACE substrates or products, namely Ang 1-7, bradykinin, bradykinin 1-5, and N-acetyl-seryl-aspartyl-lysyl-proline, did not trigger this signaling pathway. Moreover, in Tm5, a mouse melanoma cell line endogenously expressing ACE but not Ang II type 1 or type 2 receptors, Ang II increased intracellular calcium and reactive oxygen species. In conclusion, we describe for the first time that Ang II can interact with ACE and evoke calcium and other signaling molecules in cells expressing only ACE. These findings uncover a new mechanism of Ang II action and have implications for the understanding of the renin-Ang system.
Keywords:	Angiotensin I-Converting Enzyme, ACE, Calcium, Angiotensin, Cells, Receptors, Animals, Mice
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	57
Number:	5
Page Range:	965-972
Date:	May 2011
Official Publication:	https://doi.org/10.1161/HYPERTENSIONAHA.110.167171
PubMed:	View item in PubMed

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