Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8301306 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2018 | 43 Pages |
Abstract
The replacement of two consecutive histidine residues by alanine residues in the catalytic center of ceramide synthase 2 in a new transgenic mouse mutant (CerS2 H/A) leads to inactivation of catalytic activity and reduces protein level to 60% of the WT level. We show here by qRT-PCR and transcriptome analyses that several transcripts of genes involved in lipid metabolism and cell division are differentially regulated in livers of CerS2 H/A mice. Thus, very long chain ceramides produced by CerS2 are required for transcriptional regulation of target genes. The hepatocellular carcinomata previously described in old CerS2 KO mice were already present in 8-week-old CerS2 H/A animals and thus are caused by the loss of CerS2 catalytic activity already during early life.
Keywords
Flp recognition targetIBATPCNAIRES(E)GFPLoxPqRT-PCRCerSFRTTLCgWATFFATAGNBDPGKMEFDTAHEKSOEFDR(enhanced) green fluorescent proteinBACProliferating Cell Nuclear Antigensphingolipidssplicing by overlap extensionFree fatty acidsinguinal white adipose tissueGonadal white adipose tissueInterscapular brown adipose tissueTriacylglycerolsfold changeCell divisionVersusvs.diacylglycerolsDAGquantitative real time-PCRinternal ribosomal entry sitehuman embryonic kidney cellsEmbryonic stem cellsceramide synthasecytokeratinTranscription factorphosphoglycerate kinaseLipid metabolismmouse embryonic fibroblastsfalse discovery rateGene ontologyHepatocellular carcinomabacterial artificial chromosomeTranscriptional controlGlutamine synthetase
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Authors
Andreas Bickert, Paul Kern, Martina van Uelft, Stefanie Herresthal, Thomas Ulas, Katharina Gutbrod, Bernadette Breiden, Joachim Degen, Konrad Sandhoff, Joachim L. Schultze, Peter Dörmann, Dieter Hartmann, Reinhard Bauer, Klaus Willecke,