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

Cardiovascular Research
Rukhsana GulUh-Hyun Kim

Abstract

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. 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 po...Continue Reading

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Citations

Apr 25, 2012·Naunyn-Schmiedeberg's Archives of Pharmacology·Aimo KanntHeinz Gögelein
May 23, 2014·Journal of Developmental Origins of Health and Disease·J-H LeeJ P Figueroa
Jul 17, 2019·Cold Spring Harbor Perspectives in Biology·Guillaume GilbertH Llewelyn Roderick
Dec 6, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Rukhsana GulUh-Hyun Kim
Nov 8, 2018·Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences·Leila SadeghiGholamreza Dehghan

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