Molecular and Cellular Biochemistry

, Volume 369, Issue 1–2, pp 127–133 | Cite as

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

  • Kristina Mlinac
  • Klementina Fon Tacer
  • Marija Heffer
  • Damjana Rozman
  • Svjetlana Kalanj Bognar
Article
  • 236 Downloads

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.

Keywords

Gangliosides Mouse brain Cholesterol Gene expression 

Abbreviations

Cyp46

Cholesterol 24-hydroxylase

Cyp51

Lanosterol 14 alpha-demethylase

Hmgr

Hydroxymethylglutaryl-CoA reductase

Hmgs

Hydroxymethylglutaryl-CoA synthase

Insig1

Insulin induced gene 1

Insig2a

Insulin induced gene 2a

Ldlr

Low density lipoprotein receptor

Npc1

Niemann-Pick C1

Srebp1a

Sterol regulatory element-binding protein 1a

Srebp1c

Sterol regulatory element-binding protein 1c

Srebp2

Sterol regulatory element-binding protein 2

Vldlr

Very low density lipoprotein receptor

Gangliosides are abbreviated according to the system of Svennerholm [38, 39].

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Kristina Mlinac
    • 1
  • Klementina Fon Tacer
    • 2
  • Marija Heffer
    • 3
  • Damjana Rozman
    • 2
  • Svjetlana Kalanj Bognar
    • 1
  1. 1.Croatian Institute for Brain Research, School of MedicineUniversity of ZagrebZagrebCroatia
  2. 2.Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia
  3. 3.Department of Medical Biology, School of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia

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