Protective Effect of PACAP Against Doxorubicin-Induced Cell Death in cardiomyocyte Culture

Rácz, Boglárka and Reglődi, Dóra and Horváth, Gabriella and Szigeti, András and Balatonyi, Borbála and Rőth, Erzsébet and Wéber, György and Alotti, Nasri and Tóth, Gábor and Gasz, Balázs (2010) Protective Effect of PACAP Against Doxorubicin-Induced Cell Death in cardiomyocyte Culture. Journal of Molecular Neuroscience, 42 (3). pp. 419-427. ISSN 0895-8696, 1559-1166

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Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widely distributed endogenous neuropeptide, also occurring in the cardiovascular system. Among others, PACAP has been suggested as a cardioprotective factor. It has been shown that PACAP inhibits cardiac fibrosis and protects cardiomyocytes against oxidative stress and in vitro ischemia/reperfusion. The aim of the present study was to investigate whether PACAP is protective in doxorubicin-induced cell death of cardiomyocytes. Cardiomyocytes were exposed to 1 µM doxorubicin for 24 h, which resulted in a marked reduction of cell viability and a parallel increase of apoptotic cells assessed by MTT test and annexin V/propidium iodide flow cytometry assay. Co-incubation with 20 nM PACAP increased cell viability and reduced the percentage of apoptotic cells. Furthermore, doxorubicin increased the activation of caspase-3 and decreased the phosphorylation of Bad, while simultaneous PACAP treatment reduced the caspase-3 activation and increased the level of phospho-Bad. In summary, our present results demonstrate that PACAP effectively protects cardiomyocytes against doxorubicin-induced apoptotic cell death.

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