Boronkai A, Brubel R, Racz B, Tamas A, Kiss P, Horvath G, Lubics A, Szigeti A, Bellyei Sz, Toth G, Lakatos A, Reglodi D
Department of Experiemntal Zoology and Neurobiology, University of Pécs, Pécs, Hungary.
Ann N Y Acad Sci. 2009 Apr;1163:353-7. doi: 10.1111/j.1749-6632.2008.03630.x.
The pituitary adenylate cyclase activating polypeptide (PACAP) has several effects in endocrine and reproductive organs, including the placenta. PACAP is generally known as a survival-promoting peptide acting on divergent signal transduction pathways. However, its effects on the survival and signaling mechanisms of trophoblast cells are not known. In the present study we found that 1-h pretreatment with PACAP38 did not significantly influence the survival of JAR cytotrophoblast cells. However, the survival rate of cells exposed to oxidative stress or CoCl(2)-induced in vitro hypoxia showed a significant further decrease in PACAP-treated cells, implying that PACAP sensitizes the cells to these stressors. This was not observed in the case of lipopolysaccharide or ethanol treatment. Western blot data revealed that, in cells exposed to oxidative stress, PACAP treatment decreased phosphorylation of all extracellular signal-regulated kinase (ERK), phospho-jun N-terminal kinase (JNK), protein kinase B, p38 mitogen-activated protein kinase (MAPK), and phospho-glycogen synthase kinase (GSK) and the expression of bax. The overall effect seems to be a sensitizing effect in almost all examined pathways when oxidative stress was applied, which may explain the enhancing effect of PACAP on cell death in contrast to most other cell types examined so far. Our data show that the signaling mechanism of PACAP may be different in trophoblast cells to that observed in other cell lines.
垂体腺苷酸环化酶激活多肽（PACAP）在内分泌和生殖器官（包括胎盘）中具有多种作用。PACAP通常被认为是一种作用于不同信号转导途径的促存活肽。然而，其对滋养层细胞存活和信号传导机制的影响尚不清楚。在本研究中，我们发现用PACAP38预处理1小时对JAR细胞滋养层细胞的存活没有显著影响。然而，暴露于氧化应激或CoCl₂诱导的体外缺氧环境中的细胞，在PACAP处理的细胞中存活率显著进一步降低，这意味着PACAP使细胞对这些应激源敏感。在脂多糖或乙醇处理的情况下未观察到这种情况。蛋白质印迹数据显示，在暴露于氧化应激的细胞中，PACAP处理降低了所有细胞外信号调节激酶（ERK）、磷酸化c-Jun氨基末端激酶（JNK）、蛋白激酶B、p38丝裂原活化蛋白激酶（MAPK）和磷酸化糖原合酶激酶（GSK）的磷酸化水平以及bax的表达。当施加氧化应激时，总体效果似乎是在几乎所有检测的途径中都有敏化作用，这可能解释了与迄今为止检测的大多数其他细胞类型相比，PACAP对细胞死亡的增强作用。我们的数据表明，PACAP在滋养层细胞中的信号传导机制可能与在其他细胞系中观察到的不同。
