Protective effect of PACAP against doxorubicin-induced cell death in cardiomyocyte culture

Boglarka Racz, Dora Reglodi, Gabriella Horvath, Andras Szigeti, Borbala Balatonyi, Erzsebet Roth, Gyorgy Weber, Nasri Alotti, Gabor Toth, Balazs Gasz

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19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)419-427
Number of pages9
JournalJournal of Molecular Neuroscience
Volume42
Issue number3
DOIs
Publication statusPublished - Nov 1 2010

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Keywords

  • Cardiomyocyte
  • Cleaved caspase-3
  • Doxorubicin
  • Flow cytometry
  • Phospho-Bad

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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