Plasma Kallikrein and Angiotensin I-converting enzyme N- and C-terminal domain activities are modulated by the insertion/deletion polymorphism

Plasma Kallikrein and Angiotensin I-converting enzyme N- and C-terminal domain activities are modulated by the insertion/deletion polymorphism

Autor Almeida, S. S. Autor UNIFESP Google Scholar
Barros, C. C. Autor UNIFESP Google Scholar
Moraes, M. R. Autor UNIFESP Google Scholar
Russo, F. J. Autor UNIFESP Google Scholar
Haro, A. S. Autor UNIFESP Google Scholar
Rosa, T. S. Autor UNIFESP Google Scholar
Alves, M. F. Autor UNIFESP Google Scholar
Pesquero, J. B. Autor UNIFESP Google Scholar
Carmona, A. K. Autor UNIFESP Google Scholar
Bacurau, R. F. P. Google Scholar
Araujo, R. C. Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Resumo Angiotensin I-converting enzyme (ACE) is recognized as one of the main effector molecules involved in blood pressure regulation. in the last few years some polymorphisms of ACE such as the insertion/deletion (I/D) polymorphism have been described, but their physiologic relevance is poorly understood. in addition, few studies investigated if the specific activity of ACE domain is related to the I/D polymorphism and if it can affect other systems. the aim of this study was to establish a biochemical and functional characterization of the I/D polymorphism and correlate this with the corresponding ACE activity. for this purpose, 119 male brazilian army recruits were genotyped and their ACE plasma activities evaluated from the C- and N-terminal catalytic domains using fluorescence resonance energy transfer (FRET) peptides, specific for the C-domain (Abz-LFK(Dnp)OH), N-domain (Abz-SDK(Dnp)P-OH) and both C- and N-domains (Abz-FRK(Dnp)P-OH). Plasma kallikrein activity was measured using Z-Phe-Arg-AMC as substrate and inhibited by selective plasma kallikrein inhibitor (PKSI). Some physiological parameters previously described related to the I/D polymorphism such as handgrip strength, blood pressure, heart rate and BMI were also evaluated. the genotype distribution was II n = 27, ID n = 64 and DD n = 28. Total plasma ACE activity of both domains in II individuals was significantly lower in comparison to ID and DD. This pattern was also observed for C- and N-domain activities. Difference between ID and DD subjects was observed only with the N-domain specific substrate. Blood pressure, heart rate, handgrip strength and BMI were similar among the genotypes. This polymorphism also affected the plasma kallikrein activity and DD group presents high activity level. Thus, our data demonstrate that the I/D ACE polymorphism affects differently both ACE domains without effects on handgrip strength. Moreover, this polymorphism influences the kallikrein-kinin system of normotensive individuals. (C) 2009 Elsevier B.V. All rights reserved.
Palavra-chave Angiotensin I-converting enzyme
I/D polymorphism
Plasma kallikrein activity
Handgrip strength
Idioma Inglês
Data de publicação 2010-04-01
Publicado em Neuropeptides. Edinburgh: Churchill Livingstone, v. 44, n. 2, p. 139-143, 2010.
ISSN 0143-4179 (Sherpa/Romeo, fator de impacto)
Publicador Churchill Livingstone
Extensão 139-143
Fonte http://dx.doi.org/10.1016/j.npep.2009.12.003
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000276001700012
Endereço permanente http://repositorio.unifesp.br/handle/11600/32427

Exibir registro completo




Arquivo

Arquivo Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item está nas seguintes coleções

Buscar


Navegar

Minha conta