Elsevier

Redox Biology

Volume 1, Issue 1, 2013, Pages 125-130
Redox Biology

Mini Review
Oxysterols in the pathogenesis of major chronic diseases

https://doi.org/10.1016/j.redox.2012.12.001Get rights and content
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open access

Abstract

Pathological accumulation of 27-carbon intermediates or end-products of cholesterol metabolism, named oxysterols, may contribute to the onset and especially to the development of major chronic diseases in which inflammation, but also oxidative damage and to a certain extent cell death, are hallmarks and primary mechanisms of progression. Indeed, certain oxysterols exercise strong pro-oxidant and pro-inflammatory effects at concentrations detectable in the lesions typical of atherosclerosis, neurodegenerative diseases, inflammatory bowel diseases, age-related macular degeneration, and other pathological conditions characterized by altered cholesterol uptake and/or metabolism.

Research highlights

► Oxysterols are 27-carbon-atom products of enzymatic or non-enzymatic oxidation of cholesterol. ► Oxidative stress is the major non-enzymatic source of oxysterols. ► Oxysterols may in turn amplify oxidative redox imbalance in cells and tissues. ► Pathological accumulation of oxysterols triggers and sustains inflammatory reactions. ► Oxysterol-mediated inflammation is a primary mechanism of progression in major chronic diseases.

Abbreviations

α-EPOX
5α,6α-epoxycholesterol
β-EPOX
5β,6β-epoxycholesterol
7α-OH
7α-hydroxycholesterol
7β-OH
7β-hydroxycholesterol
7-K
7-ketocholesterol
24-OH
24-hydroxycholesterol
27-OH
27-hydroxycholesterol
Amyloid-β
AMD
Age-related macular degeneration
AP-1
Activator protein-1
ERK1/2
Extracellular signaling-regulated kinase 1/2
FXR
Farnesoid X receptor
IBD
Inflammatory bowel diseases
ICAM
Intercellular adhesion molecule-1
IL
Interleukin
JNK
c-Jun N-terminal
LDL
Low density lipoprotein
LXR
Liver X receptor
MAPK
Mitogen-activated protein kinase
MCP-1
Monocyte chemotactic protein-1
MIP-1β
Monocyte inflammatory protein-1β
MMP
Matrix metalloproteinase
NF-κB
Nuclear factor-κB
PKC
Protein kinase C
ROS
Reactive oxygen species
TGFβ1
Transforming growth factor β1
TIMP
Tissue inhibitors of metalloproteinases
TNF-α
Tumor necrosis factor-α
VCAM-1
Vascular cell adhesion molecule-1

Keywords

Oxysterols
Oxidative stress
Inflammation
Human chronic diseases

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