RGD Reference Report - Inhibition of ADP-ribosyl cyclase attenuates angiotensin II-induced cardiac hypertrophy. - Rat Genome Database

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Inhibition of ADP-ribosyl cyclase attenuates angiotensin II-induced cardiac hypertrophy.

Authors: Gul, R  Park, JH  Kim, SY  Jang, KY  Chae, JK  Ko, JK  Kim, UH 
Citation: Gul R, etal., Cardiovasc Res. 2009 Feb 15;81(3):582-91. Epub 2008 Aug 21.
RGD ID: 2307236
Pubmed: PMID:18719074   (View Abstract at PubMed)
DOI: DOI:10.1093/cvr/cvn232   (Journal Full-text)

AIMS: Here, we report the discovery of a small molecule inhibitor, 2,2'-dihydroxyazobenzene (DAB), of ADP ribosyl cyclase (ADPR-cyclase) and showed that this inhibitor attenuated angiotensin (Ang) II-induced hypertrophic responses. METHODS: and results The intracellular concentration of free Ca(2+) [Ca(2+)](i) in adult rat cardiomyocytes was measured by using a confocal microscope. Cardiac hypertrophy was induced by the two-kidney one-clip (2K1C) method. Hypertrophy was determined by de novo protein synthesis, cell volume, echocardiography, nuclear translocation of nuclear factor of activated T-cells, and transforming growth factor-beta1 protein expression. Treatment of cardiomyocytes with Ang II generated a biphasic [Ca(2+)](i) increase that included an initial Ca(2+)peak and sustained Ca(2+) rise via inositol trisphosphate and cyclic ADP-ribose (cADPR) formation, respectively. A cADPR antagonistic analogue, 8-Br-cADPR, and an ADPR-cyclase inhibitor, DAB, blocked the sustained Ca(2+) signal, but not the initial Ca(2+) rise. Furthermore, DAB significantly inhibited Ang II-mediated cADPR formation and hypertrophic responses in vitro. Echocardiography and histological examination revealed significant cardiac hypertrophy in 2K1C rats that was potently inhibited by treatment with DAB. In addition, the hypertrophic responses induced by Ang II in vitro were significantly increased by 2K1C, and DAB treatment reversed these hypertrophic responses to the levels of sham Control. CONCLUSION: ADPR-cyclase is an important mediator of cardiac hypertrophy, and inhibition of ADPR-cyclase by DAB may provide a new therapeutic strategy for cardiac diseases.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly  ISOCd38 (Rattus norvegicus)2307236; 2307236 RGD 
Cardiomegaly  IMP 2307236 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell growth  IMP 2307236 RGD 
positive regulation of cytosolic calcium ion concentration  IMP 2307236 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd38  (CD38 molecule)

Genes (Mus musculus)
Cd38  (CD38 antigen)

Genes (Homo sapiens)
CD38  (CD38 molecule)


Additional Information