Effects of benzo-a-pyrene on oxytocin-induced Ca2+ oscillations in myometrial cells
Effects of benzo-a-pyrene on oxytocin-induced Ca2+ oscillations in myometrial cells
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DOI：
10.1016/j.toxlet.2006.02.005
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发表时间：
2006-08-20
影响因子：
3.5
通讯作者：
Burghardt, Robert C.
中科院分区：
文献类型：
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作者：
Barhoumi, Rola;Awooda, Igbal;Burghardt, Robert C.
苯并-a-芘（BaP）是一种多环芳烃，是一种主要的环境污染物。在人子宫肌层细胞系（PHM 1）中检查了这种致癌物/诱变剂对子宫肌层Ca 2+信号传导的影响。细胞暴露于BaP不会改变基础Ca 2+水平或肌醇（1.4.5）三磷酸盐释放的Ca 2+池。然而. BaP显著降低了催产素诱导的初始Ca 2+瞬变和催产素诱导的Ca 2+振荡的频率以及延迟其发作。确定苯并（a）芘的具体作用。使用靶向细胞内Ca 2+稳态机制的药物。Genistein（一种非特异性酪氨酸激酶抑制剂）和AG 1478（所有表皮生长因子受体阻断剂）显着降低催产素诱导的Ca 2+振荡在控制。但对BaP处理的细胞没有影响。在催产素之前或之后添加表皮生长因子或血清恢复BaP处理的细胞中的Ca 2+振荡至与对照细胞相似的水平。而K通道阻断剂氯化四乙基铵。部分恢复了Ca 2+反应。这些数据表明酪氨酸激酶途径。其是PHM 1细胞中G蛋白偶联受体途径对催产素反应的一部分。是BaP作用靶点，EGF或血清Call恢复催产素诱导的Ca振荡。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Benzo-a-pyrene (BaP) is a polycyclic aromatic hydrocarbon that exists its a major environmental pollutant. The effect of this carcinogen/mutagen upon myometrial Ca2+ signaling in a human myometrial cell line (PHM1) was examined. Exposure Of Cells to BaP did not alter basal Ca2+ levels or the inositol(1.4.5) trisphosphate-releasible Ca2+ pool. However. BaP significantly decreased the initial oxytocin-induced Ca2+ transient and the frequency of oxytoxcin-induced Ca2+ Oscillations a well a delayed their onset. To determine the specific effects of BaP. pharmacologic agents that target intracellular Ca2+ homeotasis mechanisms were used. Genistein (a non-specific tyrosine kinase inhibitor) and AG1478 (all epidermal growth factor receptor blocker) markedly reduced the oxytocin-induced Ca2+ oscillations in control. but had no effect in BaP treated cells. Addition of epidermal growth factor or serum before or after oxytocin restored the Ca2+ oscillations in BaP treated cells to a level similar to control cells. while the K-channel blocker tetraethylammonium chloride. partially restored the Ca2+ response. These data that the tyrosine kinase pathway. which is part of the G-protein Coupled receptor pathway response to oxytocin in PHM1 cell. is a target of BaP action and that EGF or serum call restore the oxytocin-induced Ca oscillations. (c) 2006 Elsevier Ireland Ltd. All rights reserved.