Department of Biochemistry and Medical Chemistry, University of Pecs, Szigeti u 12, Pecs, Hungary.
J Mol Neurosci. 2010 Nov;42(3):419-27. doi: 10.1007/s12031-010-9349-6. Epub 2010 Apr 20.
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.
垂体腺苷酸环化酶激活肽（PACAP）是一种广泛分布的内源性神经肽，也存在于心血管系统中。除其他外，PACAP 已被认为是一种心脏保护因子。研究表明，PACAP 可抑制心肌纤维化，并可防止心肌细胞发生氧化应激和体外缺血/再灌注损伤。本研究旨在探讨 PACAP 是否对阿霉素诱导的心肌细胞死亡具有保护作用。将心肌细胞暴露于 1 μM 阿霉素 24 小时，MTT 试验和 Annexin V/碘化丙啶流式细胞术检测结果表明，这会导致细胞活力明显降低，凋亡细胞比例平行增加。用 20 nM PACAP 共孵育可增加细胞活力并减少凋亡细胞的百分比。此外，阿霉素增加了 caspase-3 的激活并降低了 Bad 的磷酸化水平，而同时用 PACAP 处理则降低了 caspase-3 的激活并增加了磷酸化 Bad 的水平。综上所述，我们的研究结果表明，PACAP 可有效保护心肌细胞免受阿霉素诱导的凋亡性细胞死亡。
