Cholesterol secoaldehyde induces apoptosis in J774 macrophages via mitochondrial pathway but not involving reactive oxygen species as mediators.

Full Abstract

Cholesterol secoaldehyde (3beta-hydroxy-5-oxo-5,6-secocholestan-6-al or ChSeco) is an oxysterol known to be formed in reactions of ozone with cholesterol and also when cholesterol-5alpha-hydroperoxide undergoes Hock cleavage. In view of its widespread occurrence and atherogenic potential, we examined the effects of ChSeco on mouse J774 macrophage viability and events associated with apoptosis. A dose-dependent decrease in cell viability, disruptions in mitochondrial transmembrane potential (64+/-5.5%; mean+/-SD, n=3), increased levels of cytosolic cytochrome c (8.8+/-0.84 ng/ml; mean+/-SD, n=3), activation of caspase-3 (ca. 3.6-fold) and caspase-9 (ca.1.8-fold), and increased DNA fragmentation (ca. 5-fold), all indicative of apoptosis, were observed in response to exposure to ChSeco. The apoptotic nature of cell death in macrophages was confirmed by dual staining with acridine orange and ethidium bromide. However, unlike the case with cardiomyoblasts and neuronal cells, the apoptotic process in these immune cells was not mediated by increased levels of reactive oxygen species as indicated by a minimal or no increase in 2',7'-dichlorofluorescein fluorescence. It is suggested that the apoptotic process is mediated via the mitochondrial pathway and that ChSeco formed in biological environments contributes to the initiation, progression, and culmination of atherosclerotic plaque formation, as these processes are critically dependent on macrophage apoptosis.

Author information

Author/s: Gao, Xueli (X); Raghavamenon, Achuthan C (AC); D'Auvergne, Oswald (O); Uppu, Rao M (RM);

Affiliation: Department of Environmental Toxicology, Southern University and A&M College, Baton Rouge, LA 70813, USA.

Grants: ES10018 (Agency:NIEHS NIH HHS) ; P20 RR16456 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun), published in United States. (Language: eng)

Reference: 2009-Nov; vol 389 (issue 2) : pp 382-7

Dates: Created 2009/09/29; Completed 2009/10/14;

PMID: 19733550, status: MEDLINE (last retrieval date: 10/14/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Apoptosis
Cell Line
Cholestanones - metabolism; pharmacology
Cholesterol - metabolism; pharmacology

Macrophages - drug effects; metabolism
Mice
Mitochondria - metabolism
Reactive Oxygen Species - metabolism
Secosteroids - metabolism; pharmacology

Associated Chemicals: Cholestanones (0) ; Reactive Oxygen Species (0) ; Secosteroids (0) ; Cholesterol (57-88-5) ; 3-hydroxy-5-oxo-5,6-secocholestan-6-al (81811-27-0)

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