Modulation of ceramide metabolism in mouse primary macrophages

被引:14
作者
Rovina, Philipp [1 ]
Graf, Christine [1 ]
Bornancin, Frederic [1 ]
机构
[1] Novartis Inst BioMed Res, A-1235 Vienna, Austria
关键词
Ceramide; Kinase; 1-phosphate; Glucosylceramide; Sphingomyelin; Macrophage; Activation; KINASE; GLUCOSYLCERAMIDE; MONOCYTE;
D O I
10.1016/j.bbrc.2010.07.034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Ceramide kinase (CERK) produces the bioactive lipid ceramide 1-phosphate (C1P) and is, together with glucosylceramide synthase (GCS) and sphingomyelin synthases (SMS-1 and -2), a key regulator of ceramide metabolism. Here, we used a previously validated assay for measuring CERK, GCS, and SMS activities simultaneously, to study the regulation of ceramide metabolism in mouse macrophages. Elicitation of peritoneal macrophages as well as differentiation of bone marrow-derived monocytes into macrophages led to "ceramide anabolic switching" by re-directing ceramide anabolism towards C1P synthesis by CERK. In contrast, macrophage activation by lipopolysaccharide (LPS) evoked a "ceramide anabolic switch" going in the opposite direction, i.e. featuring up-regulation of GCS and SMS and down-regulation of CERK. The LPS effects were partially blocked by dexamethasone, a known macrophage de-activator. Altogether, the data reveal a contrasting regulation of ceramide metabolism enzymes during macrophage biological responses. (c) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:150 / 154
页数:5
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