title: Ceramide metabolism in mouse tissue.
abstract: Ceramides with different N-acyl chains can act as second messengers in various signaling pathways. They are involved in cell processes such as apoptosis, differentiation and inflammation. Ceramide synthases (CerS) are key enzymes in the biosynthesis of ceramides and dihydroceramides. Six isoenzymes (CerS1-6) catalyze the N-acylation of the sphingoid bases, albeit with strictly acyl-Coenzyme A (CoA) chain length specificity. We analyzed the mRNA expression, the protein expression, the specific activity of the CerS, and acyl-CoA, dihydroceramide and ceramide levels in different tissues by LC-MS/MS. Our data indicate that each tissue express a distinct composition of CerS, whereby the CerS mRNA expression levels do not correlate with the respective protein expression levels in the tissues. Furthermore, we found a highly significant negative correlation between the protein expression level of CerS6 and the C16:0-acyl-CoA amounts as well as between the protein expression of CerS2 and C24:0-acyl-CoA amounts. These data indicate that in mouse tissues low substrate availability is compensated by higher CerS protein expression level and vice versa. Apart from the expression level and the specific activity of the CerS, other enzymes of the sphingolipid pathway also influence the composition of ceramides with distinct chain lengths in each cell. Acyl-CoA availability seems to be less important for ceramide composition and might be compensated for by CerS expression/activity.
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main 60590, Germany. Susanne.schiffmann@med.uni-frankfurt.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Schiffmann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Birod
authors.forename: Julia
authors.initials: J
authors.lastname: Männich
authors.forename: Max
authors.initials: M
authors.lastname: Eberle
authors.forename: Marthe-Susanna
authors.initials: MS
authors.lastname: Wegner
authors.forename: Ruth
authors.initials: R
authors.lastname: Wanger
authors.forename: Daniela
authors.initials: D
authors.lastname: Hartmann
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreiros
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.forename: Sabine
authors.initials: S
authors.lastname: Grösch
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002518:Ceramides / Q000096:biosynthesis / Q000378:metabolism*; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D000214:Acyl Coenzyme A; D002518:Ceramides; D012333:RNA, Messenger; D010088:Oxidoreductases; C108138:dihydroceramide desaturase
keywords: (dihydro)ceramide synthase; Acyl-CoA; Acyl-Coenzyme A; Cer; CerS; Ceramide; Ceramide synthase; LC–MS/MS; Mouse tissue; dhCer; dihydroceramide; liquid chromatography coupled with tandem mass spectrometry