7-Ketocholesterol Induces Cell Apoptosis by Activation of Nuclear Factor kappa B in Mouse Macrophages

We investigated the molecular mechanisms responsible for the induction of apoptosis in mouse mono-cytic 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-κB) was assessed by electrophoretic mobility shift assay (EMSA). Results showed that 7-KC-stimulation in J774A.1 cells activated NF-κB, 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-κB 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-κB 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-κB. Key words: 7-KC, NF-κB, apoptosis, atherosclerosis therosclerosis (AS) is a primary cause of coro-nary artery and cerebrovascular disease, 2 of the most common causes of illness and death world-wide [1]. AS is also a chronic inflammatory diseas