title: 7-ketocholesterol induces cell apoptosis by activation of nuclear factor kappa B in mouse macrophages.
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.
authors.affiliation: College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University, Dalian Economical and Technological Development Zone, Liaoning 116622, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Huang
authors.forename: Qingping
authors.initials: Q
authors.lastname: Liu
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Li
authors.forename: Renjun
authors.initials: R
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Yingbiao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chi
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.forename: Zibo
authors.initials: Z
authors.lastname: Liu
authors.forename: Qiming
authors.initials: Q
authors.lastname: Zhang
mesh_terms: 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*
chemical_list: D007653:Ketocholesterols; D016328:NF-kappa B; C003001:7-ketocholesterol