Cellular mechanisms of acrolein-induced alteration in calcium signaling in airway smooth muscle
Cellular mechanisms of acrolein-induced alteration in calcium signaling in airway smooth muscle
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DOI：
10.1006/taap.1999.8879
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发表时间：
2000-04-15
影响因子：
3.8
通讯作者：
Marthan, R
中科院分区：
文献类型：
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作者：
Hyvelin, JM;Roux, E;Marthan, R
丙烯醛是一种不饱和脂肪醛，是一种强有力的呼吸道刺激物。我们以前已经观察到，丙烯醛离体给药到离体气道改变随后的气道反应性毒蕈碱激动剂的机械活动的环和钙信号在离体细胞。在本研究中，我们研究了丙烯醛改变Ca 2+信号的机制。在新鲜分离的大鼠气管平滑肌细胞中，预先暴露于丙烯醛增加了[Ca 2 +]（i）响应内皮素1（ET-1，0.1 μ M）的振荡频率，内皮素1是一种收缩激动剂，通过激活不同于毒蕈碱胆碱受体的受体起作用。然后，我们研究了丙烯醛诱导的细胞信号传导的改变，特别关注膜受体活化的下游步骤，即，1，4，5-三磷酸肌醇（InsP（3））信号通路。用LiCl（20 mM）（InsP（3）浓度的调节剂）预处理细胞，模拟丙烯醛暴露对激动剂诱导的[Ca 2 +]（i）反应的影响，即，增加的幅度的第一个Ca 2+上升和振荡频率响应0.1和10 μ M乙酰胆碱（ACh），分别。此外，在气管平滑肌中，预先暴露于丙烯醛显着增加卡巴胆碱诱导的[H-3]肌醇-磷酸盐的积累，高达34 +/- 11%以上未暴露的组织值。最后，在β-七叶皂苷透化的细胞中，注射InsP（3）（0.1-10 μ M）诱导浓度依赖性[Ca 2 +]（i）升高，随后，对于高InsP（3）浓度，[Ca 2 +]（i）振荡，其模式类似于ACh诱导的钙响应。丙烯醛暴露不改变InsP（3）诱导的[Ca ~（2+）]（i）反应。这些结果表明，丙烯醛暴露对气道平滑肌Ca 2+反应的影响并不局限于毒蕈碱胆碱受体的激活，而是由于激动剂诱导的InsP（3）产生的增强。由于丙烯醛不改变InsP（3）受体通道的敏感性，我们得出结论，丙烯醛诱导的钙信号转导的改变可以归因于其对InsP（3）的产生的唯一影响。(C)北京大学出版社.
Acrolein, an unsaturated aliphatic aldehyde, is a potent respiratory irritant. We have previously observed that acrolein administered ex vivo to isolated airways alters subsequent airway responsiveness to muscarinic agonists in terms of both mechanical activity of rings and calcium signaling in isolated cells. In the present study, we have examined the mechanisms by which acrolein alters Ca2+ signaling. In freshly isolated rat tracheal smooth muscle cells, preexposure to acrolein increased the [Ca2+](i) oscillation frequency in response to endothelin 1 (ET-1, 0.1 mu M), a contractile agonist that acts via the activation of a receptor different from the muscarinic cholinoceptor. We then studied acrolein-induced alteration in cell signaling with special attention to the steps downstream of membrane receptor activation i.e., the inositol 1,4,5-trisphosphate (InsP(3)) signaling pathway. Pretreatment of cells with LiCl (20 mM), a modulator of InsP(3) concentration, mimicked the effect of acrolein exposure on agonist-induced [Ca2+](i) response, i.e., increased the amplitude of the first Ca2+ rise and the oscillation frequency in response to 0.1 and 10 mu M acetylcholine (ACh), respectively. Moreover, in tracheal smooth muscle, preexposure to acrolein significantly increased carbachol-induced [H-3]inositol-phosphates accumulation, up to 34 +/- 11% above unexposed tissue values. Finally, in beta-escin permeabilized cells, injection of InsP(3) (0.1-10 mu M) induced a concentration-dependent [Ca2+](i) rise followed, for high InsP(3) concentration, by [Ca2+](i) oscillations, a calcium response whose pattern was similar to that induced by ACh. Exposure to acrolein did not alter the InsP(3)-induced [Ca2+](i) response. These results indicate that the effect of acrolein exposure on Ca2+ responses in airway smooth muscle is not restricted to activation of the muscarinic cholinoceptor and is due to an enhancement in agonist-induced InsP(3) production. Since acrolein does not modify InsP(3) receptor channel sensitivity, we conclude that acrolein-induced alteration in calcium signaling can be ascribed to its sole effect on InsP(3) production. (C) 2000 Academic Press.