Adenosine protects againts angiotensin II-induced apoptosis in rat cardiocyte cultures

Ilan Goldenberg, Asher Shainberg, Kenneth A. Jacobson, Vladimir Shneyvays, Ehud Grossman

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Adenosine has been found to be cardioprotective during episodes of cardiac ischemia/reperfusion through activation of the A1 and possibly A3 receptors. Therefore, we have investigated whether activation of these receptors can protect also against apoptotic death induced by angiotensin II (Ang II) in neonatal rat cardiomyocyte cultures. Exposure to Ang II (10 nM) resulted in a 3-fold increase in programmed cell death (p < 0.05). Pretreatment with the A1 adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 1 μM), abolished the effects of Ang II on programmed cardiomyocyte death. Moreover, exposure of cells to the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) before pretreatment with CCPA, prevented the protective effect of the latter. Pretreatment with the A3 adenosine receptor agonist N6-(3-iodobenzyl) adenosine-5′-N-methyluronamide (IB-MECA, 0.1 μM), led to a partial decrease in apoptotic rate induced by Ang II. Exposure of myocytes to Ang II caused an immediate increase in the concentration of intracellular free Ca2+ that lasted 40-60 sec. Pretreatment of cells with CCPA or IB-MECA did not block Ang II-induced Cal2+ elevation. In conclusion, activation of adenosine A1 receptors can protect the cardiac cells from apoptosis induced by Ang II, while activation of the adenosine A3 receptors confers partial cardioprotection.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalMolecular and Cellular Biochemistry
Volume252
Issue number1-2
DOIs
StatePublished - Oct 2003

Bibliographical note

Funding Information:
We thank A. Isaac and T. Zinman for their valuable technical assistance and S. Victor for typing the manuscript. This study was supported in part by the Health Sciences Research Center at Bar-Ilan University.

Funding

We thank A. Isaac and T. Zinman for their valuable technical assistance and S. Victor for typing the manuscript. This study was supported in part by the Health Sciences Research Center at Bar-Ilan University.

FundersFunder number
Health Sciences Research Center at Bar-Ilan University
National Institute of Diabetes and Digestive and Kidney DiseasesZ01DK031117

    Keywords

    • A and A adenosine receptors
    • Angiotensin II
    • Apoptosis
    • Cardiomyocytes
    • Feulgen and TUNEL stainings

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