Protective effect of PACAP against doxorubicin-induced cell death in cardiomyocyte culture.
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.
Racz
Boglarka
B
Department of Biochemistry and Medical Chemistry, University of Pecs, Szigeti u 12, Pecs, Hungary. boglarka.racz@aok.pte.hu
Reglodi
Dora
D
Horvath
Gabriella
G
Szigeti
Andras
A
Balatonyi
Borbala
B
Roth
Erzsebet
E
Weber
Gyorgy
G
Alotti
Nasri
N
Toth
Gabor
G
Gasz
Balazs
B
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000737:chemistry / Q000494:pharmacology*; D020033:Protein Isoforms / Q000737:chemistry / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D020033:Protein Isoforms; D004317:Doxorubicin
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