Free Radical Attack on Cholesterol: Oxysterols as Markers of Oxidative Stress and as Bioactive Molecules

Author(s): F. Micheletta, L. Iuliano.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)

Volume 6 , Issue 3 , 2006

Abstract:

Oxysterols are oxygenated derivatives of cholesterol with a very short life-time relative to cholesterol. Oxysterols are present in nanomolar concentrations in biological fluids underscoring their role as important intermediates in a number of biochemical pathways including bile acid synthesis, reverse cholesterol transport, control of cholesterol synthesis in the brain, and oxidative stress. Most oxysterols are produced by enzymes of the cytochrome P450 family while others are produced by free radical reactions. This last group of oxysterols (stress oxysterols, or SOX) , which are mainly oxygenated in the C6 or C7 position, have attracted interest for mechanistic studies in the context of oxidative stress, and for probing oxidative stress in vivo . Sensitive and specific mass spectrometric methods have been prepared to measure SOX in a number of clinical settings, and to follow the changes induced by pharmacological treatments. Additional interest in oxidative stress oxysterols is linked to the increasing number of biological effects, obtained at cellular level and in animal models, implicated in the pathophysiological mechanisms that play a role in several diseases, including atherosclerosis, neurodegeneration, and cancer. Oxysterols have in fact been shown to induce apoptosis, cell differentiation, cytotoxicity, and impairment of endothelial function. This review is an evaluation of the recent literature on oxysterols, in particular on the role of oxysterols as bioactive compounds.

Keywords: Free radicals, antioxidants, apoptosis, cholesterol, lipid peroxidation, oxidative stress, oxysterols

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Article Details

VOLUME: 6
ISSUE: 3
Year: 2006
Page: [305 - 316]
Pages: 12
DOI: 10.2174/187152206777435618
Price: $58

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