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Sterols and gene expression: control of affluence
K Schoonjans1, C Brendel, D Mangelsdorf
1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.
Biochimica Et Biophysica Acta
|December 9, 2000
Summary
Oxysterols, signaling molecules derived from cholesterol, regulate cellular cholesterol levels. They control cholesterol uptake and utilization pathways, ensuring precise concentration maintenance.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Cellular cholesterol homeostasis is critical, maintained by complex transcriptional controls.
- Oxysterols act as signaling molecules, modulating transcription factors to prevent cholesterol overload.
Purpose of the Study:
- To elucidate the regulatory mechanisms of cholesterol homeostasis involving oxysterols.
- To highlight the roles of sterol response element binding proteins (SREBPs) and oxysterol-activated nuclear receptors.
Main Methods:
- Review of transcriptional control mechanisms.
- Analysis of oxysterol signaling pathways.
- Focus on nuclear receptors like liver X receptor (LXR) and farnesol X receptor (FXR).
Main Results:
- Oxysterols modulate SREBP activity, inhibiting cholesterol uptake and synthesis.
- Oxysterols activate nuclear receptors (LXR, SF-1) promoting cholesterol utilization.
- Bile acid synthesis and reabsorption are regulated by FXR.
Conclusions:
- Oxysterol-mediated regulation involves both feedback inhibition of cholesterol synthesis and feedforward stimulation of cholesterol utilization.
- These integrated pathways ensure fine-tuned control of intracellular cholesterol concentrations.