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

Seon Young Kim, Rukhsana Gul, So Young Rah, Hee Kim Suhn, Kwang Park Sung, Mie Jae Im, Ho Jeong Kwon, Uh Hyun Kim

Research output: Contribution to journalArticle

19 Citations (Scopus)

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-γ1. 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume294
Issue number4
DOIs
Publication statusPublished - 2008 Apr 1

Fingerprint

ADP-ribosyl Cyclase
Mesangial Cells
Angiotensin II
Cyclic ADP-Ribose
NFATC Transcription Factors
Inositol 1,4,5-Trisphosphate Receptors
Angiotensin Type 1 Receptor
1-Phosphatidylinositol 4-Kinase
Second Messenger Systems
Leucine
NAD
Protein-Tyrosine Kinases
Thymidine
Phosphorylation
Cell Proliferation
Pharmacology

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Kim, Seon Young ; Gul, Rukhsana ; Rah, So Young ; Suhn, Hee Kim ; Sung, Kwang Park ; Im, Mie Jae ; Kwon, Ho Jeong ; Kim, Uh Hyun. / Molecular mechanism of ADP-ribosyl cyclase activation in angiotensin II signaling in murine mesangial cells. In: American Journal of Physiology - Renal Physiology. 2008 ; Vol. 294, No. 4.
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Molecular mechanism of ADP-ribosyl cyclase activation in angiotensin II signaling in murine mesangial cells. / Kim, Seon Young; Gul, Rukhsana; Rah, So Young; Suhn, Hee Kim; Sung, Kwang Park; Im, Mie Jae; Kwon, Ho Jeong; Kim, Uh Hyun.

In: American Journal of Physiology - Renal Physiology, Vol. 294, No. 4, 01.04.2008.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Molecular mechanism of ADP-ribosyl cyclase activation in angiotensin II signaling in murine mesangial cells

AU - Kim, Seon Young

AU - Gul, Rukhsana

AU - Rah, So Young

AU - Suhn, Hee Kim

AU - Sung, Kwang Park

AU - Im, Mie Jae

AU - Kwon, Ho Jeong

AU - Kim, Uh Hyun

PY - 2008/4/1

Y1 - 2008/4/1

N2 - 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-γ1. 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.

AB - 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-γ1. 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.

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