7-KETOCHOLESTEROL

Description

7-keto Cholesterol is a bioactive sterol and a major oxysterol component of oxidized LDL. It is produced by oxidation of cholesterol via ethanol-mediated lipid peroxidation or photodamage as well as oxidation of 7-dehydro cholesterol by the cytochrome P450 (CYP) isoform CYP7A1. 7-keto Cholesterol inhibits CYP7A1 (IC₅₀ = ~1 μM). It induces activation and chemotaxis of retinal microglia as well as polarization to a pro-inflammatory state via NLRP3 inflammasome activation in vitro. Intraocular implantation of 7-keto cholesterol coated wafers increases ocular levels of VEGF, IL-1β, and GRO/KC, macrophage infiltration, and neovascularization in rat eye. Levels of 7-keto cholesterol in lipid deposits are increased in a variety of chronic diseases, including atherosclerosis, Alzheimer''s disease, and age-related macular degeneration.

Chemical Properties

Off-White Solid

Uses

A metabolite of Cholesterol

Uses

5-Cholesten-3β-ol-7-one was used as a standard in the determination of cholesterol derivatives by GC-MS and HPLC.

Definition

ChEBI: A cholestanoid that consists of cholesterol bearing an oxo substituent at position 7.

General Description

7-ketocholesterol is a major oxidation product of cholesterol.

Biochem/physiol Actions

7-ketocholesterol is a strong inhibitor of cytochrome P450 7A1. It modulates cholesterol homeostasis, cytotoxicity and apoptosis. 7-ketocholesterol stimulates inflammation, growth inhibition and vascular endothelial growth factor. Cellular accumulation of 7-ketocholesterol enhances oxidative stress, endoplasmic reticulum stress and apoptosis in macrophages.

Safety Profile

Questionable carcinogen with experimental tumorigenic data. When heated to decomposition it emits acrid smoke and irritating fumes