Degranulation in RBL-2H3 cells: regulation by calmodulin pathway
Degranulation in RBL-2H3 cells: regulation by calmodulin pathway
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DOI：
10.1016/s1065-6995(03)00177-x
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发表时间：
2003-01-01
影响因子：
3.9
通讯作者：
Abe, M
中科院分区：
文献类型：
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作者：
Funaba, M;Ikeda, T;Abe, M
在 RBL-2H3 肥大细胞中评估了钙调蛋白途径参与 Ca2+ 诱导的脱颗粒的情况。用钙调蛋白拮抗剂 W-13 预处理 RBL-2H3 细胞，可阻断离子霉素依赖性 β-己糖胺酶释放到上清液中，尽管单独使用 W-13 处理略有增加，但显着增加了释放。 Ca2+/钙调蛋白激活各种蛋白激酶和磷酸酶，包括肌球蛋白轻链激酶 (MLCK)、钙调蛋白依赖性蛋白激酶 (CaMK) 和钙调神经磷酸酶。当用 MLCK 抑制剂 ML-7 或 CaMKs 抑制剂 KN-93 预处理 RBL-2H3 细胞时，离子霉素依赖性 β-己糖胺酶释放到上清液中的过程受到抑制。此外，用钙调神经磷酸酶抑制剂、环孢菌素 A 和 FR901725 进行预处理，可阻断离子霉素依赖性 β-己糖胺酶释放到上清液中。我们的结果表明，Ca2+/钙调蛋白（活化的钙调蛋白）对于 Ca2+ 诱导的脱颗粒是必不可少的，并且在钙调蛋白途径中，至少 MLCK、CaMKs 和钙调磷酸酶正向调节 RBL-2H3 细胞中通过增加胞质 Ca2+ 浓度而引发的颗粒释放。 (C) 2003 Elsevier Ltd. 保留所有权利。
Involvement of the calmodulin pathway in Ca2+-induced degranulation was evaluated in RBL-2H3 mast cells. Pretreatment of RBL-2H3 cells with a calmodulin antagonist, W-13, blocked ionomycin-dependent release of beta-hexosaminidase into the supernatant, although W-13 treatment alone slightly but significantly increased the release. Ca2+/calmodulin activates various protein kinases and phosphatases including myosin-light chain kinase (MLCK), calmodulin-dependent protein kinases (CaMKs), and calcineurin. When RBL-2H3 cells were pretreated with a MLCK inhibitor, ML-7, or a CaMKs inhibitor, KN-93, the ionomycin-dependent release of beta-hexosaminidase into the supernatant was inhibited. In addition, pretreatment with calcineurin inhibitors, cyclosporin A and FR901725, resulted in blockage of the ionomycin-dependent release of beta-hexosaminidase into the supernatant. Our results indicate that Ca2+/calmodulin, activated calmodulin, is indispensable for Ca2+-induced degranulation, and that within the calmodulin pathways, at least MLCK, CaMKs and calcineurin positively regulate the release of granules initiated by increasing cytosolic Ca2+ concentrations in RBL-2H3 cells. (C) 2003 Elsevier Ltd. All rights reserved.