Inactivation of ceramide synthase 2 catalytic activity in mice affects transcription of genes involved in lipid metabolism and cell division
| Autor: | Andreas Bickert, Stefanie Herresthal, Dieter Hartmann, Martina van Uelft, Reinhard Bauer, Joachim Degen, Peter Dörmann, Konrad Sandhoff, Thomas Ulas, Klaus Willecke, Paul Kern, Bernadette Breiden, Katharina Gutbrod, Joachim L. Schultze |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Genetically modified mouse Carcinoma Hepatocellular Cell division Mice Transgenic Ceramides Transcriptome Mice 03 medical and health sciences Sphingosine N-Acyltransferase Transcriptional regulation Animals Molecular Biology Histidine Chemistry Gene Expression Profiling Liver Neoplasms Age Factors Ceramide synthase 2 Lipid metabolism Cell Biology Lipid Metabolism Sphingolipid Cell biology Gene Expression Regulation Neoplastic Mice Inbred C57BL 030104 developmental biology Liver Mutation Cell Division |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1863:734-749 |
| ISSN: | 1388-1981 |
| DOI: | 10.1016/j.bbalip.2018.04.006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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