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 language | English |
|---|---|
| Pages (from-to) | F982-F989 |
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 294 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2008 Apr 1 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Urology
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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; Ho, Jeong Kwon; Kim, Uh Hyun.
In: American Journal of Physiology - Renal Physiology, Vol. 294, No. 4, 01.04.2008, p. F982-F989.Research output: Contribution to journal › Article
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 - Ho, Jeong Kwon
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.
UR - http://www.scopus.com/inward/record.url?scp=44949233822&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44949233822&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00483.2007
DO - 10.1152/ajprenal.00483.2007
M3 - Article
C2 - 18272599
AN - SCOPUS:44949233822
VL - 294
SP - F982-F989
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 1931-857X
IS - 4
ER -