Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice -: art. no. 4
Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice -: art. no. 4
复制标题
DOI：
10.1186/1465-9921-6-4
复制
发表时间：
2005-01-08
影响因子：
5.8
通讯作者：
Misawa, M
中科院分区：
文献类型：
--
作者：
Chiba, Y;Ueno, A;Misawa, M
背景资料：最近有人提出，RhoA在增强平滑肌收缩的Ca 2+敏化中起重要作用。在本研究中，RhoA介导的钙离子敏化的参与增强支气管平滑肌（BSM）收缩在小鼠过敏性asthma models.Methods：卵白蛋白（OA）致敏的BALB/c小鼠反复挑战雾化OA和处死后24小时最后抗原的挑战。结果：OA致敏小鼠BSM对乙酰胆碱（ACh）产生高反应，但对高K+去极化无反应。在α-毒素透化的BSMs中，ACh诱导了对肉毒梭菌C3外切酶敏感的收缩的Ca 2+敏化，这表明RhoA与这种Ca 2+敏化有关。有趣的是，乙酰胆碱诱导的，RhoA介导的Ca 2+敏化显着增强OA挑战小鼠的透化BSMs。结论：抗原诱导的气道高反应性中，Ca 2+敏感效应增强，RhoA蛋白表达上调，可能参与了抗原诱导的气道高反应性中BSM收缩增强的机制。
Background: It has recently been suggested that RhoA plays an important role in the enhancement of the Ca2+ sensitization of smooth muscle contraction. In the present study, a participation of RhoA-mediated Ca2+ sensitization in the augmented bronchial smooth muscle ( BSM) contraction in a murine model of allergic asthma was examined.Methods: Ovalbumin (OA)-sensitized BALB/c mice were repeatedly challenged with aerosolized OA and sacrificed 24 hours after the last antigen challenge. The contractility and RhoA protein expression of BSMs were measured by organ-bath technique and immunoblotting, respectively.Results: Repeated OA challenge to sensitized mice caused a BSM hyperresponsiveness to acetylcholine (ACh), but not to high K+- depolarization. In alpha-toxin-permeabilized BSMs, ACh induced a Ca2+ sensitization of contraction, which is sensitive to Clostridium botulinum C3 exoenzyme, indicating that RhoA is implicated in this Ca2+ sensitization. Interestingly, the ACh-induced, RhoA-mediated Ca2+ sensitization was significantly augmented in permeabilized BSMs of OA-challenged mice. Moreover, protein expression of RhoA was significantly increased in the hyperresponsive BSMs.Conclusion: These findings suggest that the augmentation of Ca2+ sensitizing effect, probably via an up-regulation of RhoA protein, might be involved in the enhanced BSM contraction in antigen-induced airway hyperresponsiveness.