Glycosphingolipid deficiency increases the sterol regulatory element-mediated gene transcription

Reiko Ishitsuka; Yoshio Hirabayashi; Toshihide Kobayashi

doi:10.1016/j.bbrc.2008.11.030

Glycosphingolipid deficiency increases the sterol regulatory element-mediated gene transcription

Biochem Biophys Res Commun. 2009 Jan 9;378(2):240-3. doi: 10.1016/j.bbrc.2008.11.030. Epub 2008 Nov 17.

Authors

Reiko Ishitsuka¹, Yoshio Hirabayashi, Toshihide Kobayashi

Affiliation

¹ Lipid Biology Laboratory, RIKEN (Institute of Physical and Chemical Research) Advanced Science Institute, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan.

PMID: 19017528
DOI: 10.1016/j.bbrc.2008.11.030

Abstract

A major feedback mechanism of cholesterol in transcription of cholesterol metabolism-related genes is mediated by sterol regulatory element-binding protein (SREBP). Involvement of glycosphingolipids (GSLs) in the SREBP pathway is unknown. In this study, we examined the effects of GSL depletion on SRE-mediated gene transcription using GSL-defective cells. We found that the content of mature SREBP, the transcriptional active form, is increased in the GSL-defective cells. Transcription of SREBP target genes and cholesterol synthesis are also induced in the GSL-defective cells. These results indicate that GSL deficiency up-regulates the SREBP pathway, pointing out the regulatory role of GSL in cholesterol homeostasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Cholesterol / biosynthesis*
Cholesterol / genetics
Gene Expression Regulation*
Glycosphingolipids / deficiency*
Mice
Regulatory Elements, Transcriptional
Sterol Regulatory Element Binding Protein 1 / metabolism*
Sterol Regulatory Element Binding Protein 2 / metabolism*
Transcription, Genetic

Substances

Glycosphingolipids
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Protein 2
Cholesterol