TY - JOUR
T1 - A high dose of ionizing radiation induces tissue-specific activation of nuclear factor-κB in vivo
AU - Zhou, Daohong
AU - Brown, Stephen A.
AU - Yu, Tao
AU - Chen, Gang
AU - Barve, Shirish
AU - Kang, Bann C.
AU - Thompson, John S.
PY - 1999/6
Y1 - 1999/6
N2 - Activation of the transcription factor nuclear factor-κB (NF-κB) is one of the important responses of cells to an external stress such as ionizing radiation. We studied radiation-induced NF-κB activation in vivo in male BALB/c mice. After the mice were exposed to 8.5 Gy total-body γ 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-κB 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-κB 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-κB in the liver and lung. The gel supershift assay with Nfkb1, Rela and/or Rel antibodies revealed that the specific molecular forms of NF-κB activated by radiation in the spleen were Nfkb1 homodimers and Nfkb1/Rela heterodimers. In mesenteric lymph nodes, the heterodimerized Rel/Rela NF-κB was also activated. In bone marrow, an NF-κB-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-κB activation that varies in both tissue distribution and molecular composition.
AB - Activation of the transcription factor nuclear factor-κB (NF-κB) is one of the important responses of cells to an external stress such as ionizing radiation. We studied radiation-induced NF-κB activation in vivo in male BALB/c mice. After the mice were exposed to 8.5 Gy total-body γ 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-κB 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-κB 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-κB in the liver and lung. The gel supershift assay with Nfkb1, Rela and/or Rel antibodies revealed that the specific molecular forms of NF-κB activated by radiation in the spleen were Nfkb1 homodimers and Nfkb1/Rela heterodimers. In mesenteric lymph nodes, the heterodimerized Rel/Rela NF-κB was also activated. In bone marrow, an NF-κB-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-κB activation that varies in both tissue distribution and molecular composition.
UR - http://www.scopus.com/inward/record.url?scp=0032977359&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032977359&partnerID=8YFLogxK
U2 - 10.2307/3580209
DO - 10.2307/3580209
M3 - Article
C2 - 10360790
AN - SCOPUS:0032977359
SN - 0033-7587
VL - 151
SP - 703
EP - 709
JO - Radiation Research
JF - Radiation Research
IS - 6
ER -