HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/F982    most recent 00483.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, S.-Y. Articles by Kim, U.-H. Search for Related Content PubMed PubMed Citation Articles by Kim, S.-Y. Articles by Kim, U.-H.

Molecular mechanism of ADP-ribosyl cyclase activation in angiotensin II signaling in murine mesangial cells

Departments of ¹Biochemistry, ²Physiology, and ³Internal Medicine and ⁵Institute of Cardiovascular Research, Chonbuk National University Medical School, Jeonju; and ⁴Department of Biotechnology, College of Engineering, Yonsei University, Seoul, Republic of Korea

Submitted 16 October 2007 ; accepted in final form 5 February 2008

ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca²⁺-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 Ca²⁺ concentrations through a transient Ca²⁺ release via an inositol 1,4,5-trisphosphate receptor and a sustained Ca²⁺ influx via L-type Ca²⁺ channels. The sustained Ca²⁺ signal, but not the transient Ca²⁺ 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-1. 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 [³H]thymidine and [³H]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.

cyclic ADP-ribose; intracellular Ca²⁺ concentration

This article has been cited by other articles:

				R. Gul, J.-H. Park, S.-Y. Kim, K. Y. Jang, J.-K. Chae, J.-K. Ko, and U.-H. Kim Inhibition of ADP-ribosyl cyclase attenuates angiotensin II-induced cardiac hypertrophy Cardiovasc Res, October 20, 2008; (2008) cvn232v3. [Abstract] [Full Text] [PDF]