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High-throughput Nitrobenzoxadiazole-labeled Cholesterol Efflux Assay
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Cell Plasma Membrane Cholesterol as a Diagnostic.

Li Li1, Binyu Lu1, Dechen Jiang2

  • 1Department of Chemistry, Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, USA.

Current Opinion in Electrochemistry
|August 1, 2017
PubMed
Summary
This summary is machine-generated.

Active cholesterol, unbound in the plasma membrane, regulates cellular cholesterol homeostasis. This "active" form influences gene expression and metabolic processes, offering a new diagnostic target for cholesterol-related diseases.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Cholesterol is a critical structural component of the cell plasma membrane (PM), regulating biomolecular processes.
  • PM cholesterol influences protein activity and cellular cholesterol homeostasis through direct and indirect effects.
  • An excess of cholesterol in the PM can lead to an "active cholesterol" state.

Purpose of the Study:

  • To define and investigate the role of "active cholesterol" in cellular cholesterol homeostasis.
  • To explore the regulatory mechanisms involving active cholesterol in gene expression and metabolic pathways.
  • To describe a method for determining active cholesterol levels in the PM.

Main Methods:

  • Investigated the concept of "active cholesterol" as PM cholesterol not complexed with lipids.
  • Examined the regulatory role of active cholesterol in cellular cholesterol homeostasis.
  • Described a method for the determination of active cholesterol in human disease states.

Main Results:

  • Active cholesterol, present above a threshold mole fraction, acts as a regulatory control for cellular cholesterol homeostasis.
  • This active cholesterol state is recognized by membrane-bound proteins, activating genes for cholesterol synthesis enzymes.
  • Active cholesterol levels are linked to LDL uptake, HDL production/release, and cholesterol storage.

Conclusions:

  • Active cholesterol is a key regulator of cellular cholesterol homeostasis.
  • The determination of active cholesterol levels is relevant for understanding and diagnosing human diseases associated with altered PM cholesterol.
  • This research provides a framework for understanding cholesterol's dynamic role beyond its structural function.