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Acta Med Okayama. 2010 Apr;64(2):85-93.

7-ketocholesterol induces cell apoptosis by activation of nuclear factor kappa B in mouse macrophages.

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1
College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University, Dalian Economical and Technological Development Zone, Liaoning 116622, China.

Abstract

We investigated the molecular mechanisms responsible for the induction of apoptosis in mouse monocytic macrophage cell line J774A.1 stimulated by 7-ketocholesterol (7-KC). Cell apoptosis was detected by Annexin V-propidium iodide (PI) staining. The DNA-binding activity of nuclear factor kappa B (NF-kappaB) was assessed by electrophoretic mobility shift assay (EMSA). Results showed that 7-KC-stimulation in J774A.1 cells activated NF-kappaB, which is involved in cell apoptosis, in a time- and dose-dependent manners. 7-KC was also found to increase the binding activity of NF-kappaB to specific DNA binding sites, a possible mechanism for the induction of the cell apoptosis. Moreover, these effects were partially inhibited by pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. Taken together, 7-KC may be an important factor in atherosclerosis due to the ability of 7-KC to induce cell apoptosis, which is at least partially mediated through the activation of NF-kappaB.

PMID:
20424663
DOI:
10.18926/AMO/32848
[Indexed for MEDLINE]
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