Molecular mechanism of ADP-ribosyl cyclase activation in angiotensin II signaling in murine mesangial cells.
Am J Physiol Renal Physiol
; 294(4): F982-9, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18272599
ABSTRACT
ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca(2+)-mobilizing second messenger cyclic ADP-ribose (cADPR) from NAD(+). In this study, we investigated the molecular basis of ADPR-cyclase activation and the following cellular events in angiotensin II (ANG II) signaling in mouse mesangial cells (MMCs). Treatment of MMCs with ANG II induced an increase in intracellular Ca(2+) concentrations through a transient Ca(2+) release via an inositol 1,4,5-trisphosphate receptor and a sustained Ca(2+) influx via L-type Ca(2+) channels. The sustained Ca(2+) signal, but not the transient Ca(2+) signal, was blocked by a cADPR antagonistic analog, 8-bromo-cADPR (8-Br-cADPR), and an ADPR-cyclase inhibitor, 4,4'-dihydroxyazobenzene (DHAB). In support of the results, ANG II stimulated cADPR production in a time-dependent manner, and DHAB inhibited ANG II-induced cADPR production. Application of pharmacological inhibitors revealed that activation of ADPR-cyclase by ANG II involved ANG II type 1 receptor, phosphoinositide 3-kinase, protein tyrosine kinase, and phospolipase C-gamma1. Moreover, DHAB as well as 8-Br-cADPR abrogated ANG II-mediated Akt phosphorylation, nuclear translocation of nuclear factor of activated T cell, and uptake of [(3)H]thymidine and [(3)H]leucine in MMCs. These results demonstrate that ADPR-cyclase in MMCs plays a pivotal role in ANG II signaling for cell proliferation and protein synthesis.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Angiotensina II
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Cálcio
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ADP-Ribosil Ciclase
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Mesângio Glomerular
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article