engleski

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

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 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 knockout mice compared to wild-type 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 wild- type animals. Cyp46 expression was expectedly brain-specific, with brain region difference in both wild-type and St8sia1 knockout mice. 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.

gangliosides; mouse brain; cholesterol; gene expression

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