NF-kappa B, cytokines, proteasomes, and low-dose radiation exposure.
Ionizing radiation shares with proinflammatory cytokines a pathway that involves reactive oxygen species and activation of the redox-sensitive nuclear transcription factor NF-kappa B, which leads to expression of inflammatory and cell survival programs. NF-kappa B activation normally requires phosphorylation of its inhibitor I kappa B and the inhibitor's subsequent degradation by the proteasome. Nonlinear dose-response curves have been reported for both radiation-induced cytokines and NF-kappa B and I kappa B expression with maximum exposures of less than 2 Gy and greater than 4 Gy, respectively. Radiation-inhibited proteasomes function over a wide dose range, suggesting that the proteasome is a redox-sensitive target for radiation that may function along with transcription to cause nonlinear dose-response relationships for early expression of many molecules, including NF-kappa B and cytokines. These pathways are relevant to low-dose radiation effects, adaptive responses, and carcinogenesis.
McBride
William H
WH
Roy E. Coats Laboratories, Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA 90064, USA.
Pajonk
Frank
F
Chiang
Chi-Shuin
CS
Sun
Ji-Rong
JR
D000818:Animals; D003546:Cysteine Endopeptidases; D016207:Cytokines; D051379:Mice; D009097:Multienzyme Complexes; D016328:NF-kappa B; D046988:Proteasome Endopeptidase Complex; D011829:Radiation Dosage
D016207:Cytokines; D009097:Multienzyme Complexes; D016328:NF-kappa B; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex