Cholesterogenic genes expression in brain and liver of ganglioside- deficient mice

Kristina Mlinac, Klementina Fon Tacer, Marija Heffer, Damjana Rozman, Svjetlana Kalanj Bognar

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study was to determine the effect of changed ganglioside profile on transcription of selected genes involved in cholesterol homeostasis. For that purpose, the expression of 11 genes related to cholesterol synthesis, regulation, and cholesterol transport was investigated in selected brain regions (frontal cortex, hippocampus, brain stem, cerebellum) and liver of St8sia1 knockout (KO) mice characterized by deficient synthesis of b- and c-series gangliosides and accumulation of a-series gangliosides. The expression of majority of the analyzed genes, as determined using quantitative real time PCR, was slightly higher in St8sia1 KO compared to wild-type (wt) controls. More prominent changes were observed in Hmgr, Cyp51, and Cyp46 expression in brain (hippocampus and brain stem) and Srebp1a, Insig2a, and Ldlr in liver. In addition, the expression of master transcriptional regulators, Srebp1a, Srebp1c, and Insig2a, as well as transporters Ldlr and Vldlr differed between liver and brain, and within brain regions in wt animals. Cyp46 expression was expectedly brain-specific, with brain region difference in both wt and St8sia1 KO. The established change in transcriptome of cholesterogenic genes is associated to specific alteration of ganglioside composition which indicates relationship between gangliosides and regulation of cholesterol metabolism.

Original languageEnglish (US)
Pages (from-to)127-133
Number of pages7
JournalMolecular and Cellular Biochemistry
Volume369
Issue number1-2
DOIs
StatePublished - Oct 1 2012

Keywords

  • Cholesterol
  • Gangliosides
  • Gene expression
  • Mouse brain

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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