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

B. Rácz, D. Reglodi, Gabriella Horvath, A. Szigeti, Borbala Balatonyi, E. Rőth, G. Wéber, Nasri Alotti, G. Tóth, B. Gasz

Research output: Article

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. 2010

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Pituitary Adenylate Cyclase-Activating Polypeptide
Cardiac Myocytes
Doxorubicin
Cell Death
Caspase 3
Cell Survival
Propidium
Annexin A5
Cardiovascular System
Neuropeptides
Reperfusion
Flow Cytometry
Oxidative Stress
Fibrosis
Ischemia
Phosphorylation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

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title = "Protective effect of PACAP against doxorubicin-induced cell death in cardiomyocyte culture",
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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author = "B. R{\'a}cz and D. Reglodi and Gabriella Horvath and A. Szigeti and Borbala Balatonyi and E. Rőth and G. W{\'e}ber and Nasri Alotti and G. T{\'o}th and B. Gasz",
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T1 - Protective effect of PACAP against doxorubicin-induced cell death in cardiomyocyte culture

AU - Rácz, B.

AU - Reglodi, D.

AU - Horvath, Gabriella

AU - Szigeti, A.

AU - Balatonyi, Borbala

AU - Rőth, E.

AU - Wéber, G.

AU - Alotti, Nasri

AU - Tóth, G.

AU - Gasz, B.

PY - 2010/11

Y1 - 2010/11

N2 - 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.

AB - 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.

KW - Cardiomyocyte

KW - Cleaved caspase-3

KW - Doxorubicin

KW - Flow cytometry

KW - Phospho-Bad

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