Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling

Author(s):Show less -

Guimaraes, Paola B. ^[1] ; Alvarenga, Erika C. ^[1] ; Siqueira, Paula D. ^[1] ; Paredes-Gamero, Edgar J. ^[1] ; Sabatini, Regiane A. ^[1] ; Morais, Rafael L. T. ^[1] ; Reis, Rosana I. ^[2] ; Santos, Edson L. ^[3] ; Teixeira, Luis G. D. ^[1] ; Casarini, Dulce E. ^[4] ; Martin, Renan P. ^[1] ; Shimuta, Suma I. ^[1] ; Carmona, Adriana K. ^[1] ; Nakaie, Clovis R. ^[1] ; Jasiulionis, Miriam G. ^[5] ; Ferreira, Alice T. ^[1] ; Pesquero, Jorge L. ; Oliveira, Suzana M. ^[1] ; Bader, Michael ^[6] ; Costa-Neto, Claudio M. ^[2] ; Pesquero, Joao B. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biofis, BR-04023062 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Sao Paulo - Brazil

^[3] Fundacao Univ Fed Grande Dourados, Fac Ciencias Biol & Ambientais, Mato Grosso - Brazil

^[4] Univ Fed Sao Paulo, Dept Med, BR-04023062 Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo, Dept Farmacol, BR-04023062 Sao Paulo - Brazil

^[6] Max Delbruck Ctr Mol Med, Berlin - Germany

• Document type: Journal article
• Source: Hypertension; v. 57, n. 5, p. 965-U200, MAY 2011.
• Web of Science Citations: 17

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. (Hypertension. 2011;57:965-972.) . Online Data Supplement (AU)

• FAPESP's process: 02/00807-7 - Cell and molecular biology of the renin-antiotensin and kalikrein-kinins systems
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants