Physiological functions of oxysterols, the oxidized derivatives of cholesterol that act as crucial signaling molecules:

Oxysterol Associated Diseases and Disorders

Oxysterols – Physiological Functions

Oxysterols are oxygenated forms of cholesterol, either enzymatically or non-enzymatically produced, with key roles in cholesterol homeostasis, immune response, and cell signaling.

Order Oxysterol Kit

Oxysterol Pathway Profiling Kit
Quick View

Oxysterol Pathway Profiling Kit

$1,995.00
Add to cart

Regulation of Cholesterol Homeostasis

  • Oxysterols provide feedback inhibition of cholesterol synthesis:
    • Inhibit HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis)
    • Suppress SREBP-2 activation, reducing cholesterol biosynthetic gene expression

Key Oxysterols:

  • 24(S)-hydroxycholesterol
  • 25-hydroxycholesterol
  • 27-hydroxycholesterol

Ligands for Nuclear Receptors (LXRs)

  • Oxysterols are natural activators of Liver X Receptors (LXRα and LXRβ).

LXR activation leads to:

  • Reverse cholesterol transport: ↑ABCA1, ABCG1 → promotes cholesterol efflux from cells
  • Regulation of lipid metabolism: ↓cholesterol uptake, ↑cholesterol excretion
  • Anti-inflammatory effects: Repress NF-κB-mediated cytokine production

Brain Cholesterol Turnover

  • 24(S)-hydroxycholesterol is the major cholesterol excretion product from the brain.
  • Helps maintain brain cholesterol balance, which is essential since cholesterol cannot cross the blood-brain barrier easily.

Immune System Modulation

  • 25-hydroxycholesterol plays a key role in innate immunity:
    • Inhibits viral replication (e.g., influenza, HIV, SARS-CoV-2)
    • Regulates interferon-stimulated genes
    • Modulates B cell function and antibody production

Bile Acid Synthesis

  • Some oxysterols, like 27-hydroxycholesterol, serve as intermediates in bile acid synthesis in the liver via the alternative pathway.

Apoptosis and Cell Cycle Control

  • Under certain conditions, oxysterols can:
    • Induce cell cycle arrest
    • Trigger apoptosis via oxidative stress mechanisms

Summary Table

Function

Oxysterols Involved

Regulate cholesterol synthesis

25-OHC, 27-OHC

Activate LXR and lipid metabolism

24(S)-OHC, 27-OHC, 22(R)-OHC

Brain cholesterol turnover

24(S)-OHC

Immune modulation & antiviral response

25-OHC

Bile acid synthesis intermediate

27-OHC

Apoptosis and redox signaling

7-ketocholesterol, 7β-hydroxycholesterol