Ceramide induces serotonin release from RBL-2H3 mast cells through calcium mediated activation of phospholipase A2

被引:9
作者
Ji, Jung Eun [1 ]
Kim, Seok Kyun [1 ]
Ahn, Kyong Hoon [1 ]
Choi, Jong Min [1 ]
Jung, Sung Yun [1 ]
Jung, Kwang Mook [1 ]
Jeon, Hyung Jun [1 ]
Kim, Dae Kyong [1 ]
机构
[1] Chung Ang Univ, Coll Pharm, Dept Environm & Hlth Chem, Seoul 156756, South Korea
关键词
Ceramide; Calcium; Mast cells; Degranulation; Arachidonic acid; Ceramide kinase; Phospholipase A(2); GROUP-II PHOSPHOLIPASE-A2; ARACHIDONIC-ACID; CYTOSOLIC PHOSPHOLIPASE-A(2); DEPENDENT DEGRANULATION; LIPID KINASE; 1-PHOSPHATE; EXOCYTOSIS; ENZYMES; FUSION; DIFFERENTIATION;
D O I
10.1016/j.prostaglandins.2011.01.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ceramide has been suggested to function as a mediator of exocytosis in response to the addition of a calcium ionophore from PC12 cells. Here, we show that although cell-permeable C-6-ceramide or a calcium ionophore alone did not increase either the degranulation of serotonin or the release of arachidonic acid (AA) from RBL-2H3 cells, their combined effect significantly stimulated these processes in a time- and dose-dependent manner. This effect was inhibited by the presence of an exogenous calcium chelator and significantly suppressed by the CERK inhibitor (K1) and phospholipase A(2) (PLA(2)) inhibitors. Moreover, cytosolic PLA(2) GIVA (cPLA(2) GIVA) siRNA-transfected RBL-2H3 cells showed a lower level of serotonin release than scramble siRNA-transfected cells. Little is known about the regulation of degranulation proximal to the activation of cytosolic phospholipase A(2) GIVA, the initial rate-limiting step in RBL-2H3 cells. In this study, we suggest that CERK, ceramide-1-phosphate, and PLA(2) are involved in degranulation in a calcium-dependent manner. Inhibition of p44/p42 mitogen-activated protein kinase partially decreased the M release, but did not affect degranulation. Furthermore, treatment of the cells with AA (omega-6, C20:4), not linoleic acid (omega-6, C18:2) or alpha-linolenic acid (omega-6, C18:3). induced degranulation. Taken together, these results suggest that ceramide is involved in mast cell degranulation via the calcium-mediated activation of PLA(2). (C) 2011 Published by Elsevier
引用
收藏
页码:88 / 95
页数:8
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