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 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.
Huang
Zhenyu
Z
College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University, Dalian Economical and Technological Development Zone, Liaoning 116622, China.
Liu
Qingping
Q
Li
Wenzhe
W
Wang
Renjun
R
Wang
Dan
D
Zhang
Yingbiao
Y
Zhang
Fan
F
Chi
Yan
Y
Liu
Zhe
Z
Matsuura
Eiji
E
Liu
Zibo
Z
Zhang
Qiming
Q
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D007653:Ketocholesterols / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*
D007653:Ketocholesterols; D016328:NF-kappa B; C003001:7-ketocholesterol