Effects of Pituitary Adenylate Cyclase Activating Polypeptide on the Survival and Signal Transduction Pathways in Human Choriocarcinoma Cells
Effects of Pituitary Adenylate Cyclase Activating Polypeptide on the Survival and Signal Transduction Pathways in Human Choriocarcinoma Cells
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DOI：
10.1111/j.1749-6632.2008.03630.x
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Reglodi, D.
中科院分区：
文献类型：
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作者：
Boronkai, A.;Brubel, R.;Reglodi, D.
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通常被认为是一种促进存活的肽，作用于不同的信号转导途径。然而，其对滋养层细胞的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，1小时的预处理与PACAP 38没有显着影响的存活率的细胞滋养层细胞。然而，暴露于氧化应激或氯化钴诱导的体外缺氧的细胞的存活率显示出显着的进一步减少，在PACAP处理的细胞，这意味着PACAP敏感的细胞，这些压力。这在脂多糖或乙醇处理的情况下没有观察到。Western blot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jun N-末端激酶（JNK）、蛋白激酶B、p38丝裂原活化蛋白激酶（MAPK）和磷酸化糖原合成酶激酶（GSK）的磷酸化以及bax的表达。当施加氧化应激时，几乎所有检查的途径中的总体效果似乎是敏化作用，这可以解释PACAP与迄今为止检查的大多数其他细胞类型相比对细胞死亡的增强作用。我们的数据表明，PACAP的信号转导机制可能是不同的滋养层细胞中观察到的其他细胞系。
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 CoCl2-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), phosphojun 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.