Inactivation of ceramide synthase 2 catalytic activity in mice affects transcription of genes involved in lipid metabolism and cell division

Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Jul;1863(7):734-749. doi: 10.1016/j.bbalip.2018.04.006. Epub 2018 Apr 10.

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: Cell division; Ceramide synthase 2; Hepatocellular carcinoma; Lipid metabolism; Sphingolipids; Transcriptional control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Division / genetics*
  • Ceramides / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Lipid Metabolism / genetics*
  • Liver / pathology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Sphingosine N-Acyltransferase / genetics*
  • Sphingosine N-Acyltransferase / metabolism

Substances

  • Ceramides
  • Cers2 protein, mouse
  • Sphingosine N-Acyltransferase