title: A high dose of ionizing radiation induces tissue-specific activation of nuclear factor-kappaB in vivo.
abstract: Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) is one of the important responses of cells to an external stress such as ionizing radiation. We studied radiation-induced NF-kappaB activation in vivo in male BALB/c mice. After the mice were exposed to 8.5 Gy total-body gamma irradiation, the spleen, mesenteric lymph nodes, thymus, liver, lung, colon, brain and bone marrow were harvested 1, 2.5, 5, 10 and 20 h postirradiation. NF-kappaB DNA-binding activity was analyzed in the nuclear protein extracts by a gel shift assay. When compared to the levels in untreated control mice, radiation induced activation of NF-kappaB in spleen, mesenteric lymph nodes and bone marrow but not in the other tissues examined. In contrast, an i.p. injection of a lethal dose (3 mg/kg) of lipopolysaccharide also increased activity of NF-kappaB in the liver and lung. The gel supershift assay with Nfkb1, Rela and/or Rel antibodies revealed that the specific molecular forms of NF-kappaB activated by radiation in the spleen were Nfkb1 homodimers and Nfkb1/Rela heterodimers. In mesenteric lymph nodes, the heterodimerized Rel/Rela NF-kappaB was also activated. In bone marrow, an NF-kappaB-like binding factor was induced that may be Nfkb1/Rela- and Rel/Rela-like heterodimers, but it exhibited a higher mobility than Nfkb1 homodimers. These results indicate that in vivo, ionizing radiation induces NF-kappaB activation that varies in both tissue distribution and moleoular composition.
authors.affiliation: Department of Internal Medicine, University of Kentucky, Lexington 40536, USA.
authors.forename: D
authors.initials: D
authors.lastname: Zhou
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: T
authors.initials: T
authors.lastname: Yu
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Barve
authors.forename: B C
authors.initials: BC
authors.lastname: Kang
authors.forename: J S
authors.initials: JS
authors.lastname: Thompson
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism / Q000528:radiation effects*; D009928:Organ Specificity; D014916:Whole-Body Irradiation
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D004247:DNA