Document Detail


Post-translational modification of I-kappa B alpha activates NF-kappa B in human monocytes exposed to 56Fe ions.
MedLine Citation:
PMID:  12201057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The objective of this study was to investigate whether heavy ion (56Fe) radiation exposure activates one of the key transcriptional regulators, nuclear factor-kappa B (NF-kappa B), in normal human monocytes (Mono Mac 6 cells: MM6). The study revealed that the exposure of MM6 cells to 56Fe ions resulted in increased NF-kappa B DNA-binding activity. The activation was both dose- and time-dependent, with a maximum response at the 2 h time point after a 0.7 Gy dose. Cells pre-incubated with inhibitors of the phosphorylation and proteasome signaling pathway, completely blocked heavy ion-induced activation of NF-kappa B. These results clearly indicate that 56Fe ions can induce NF-kappa B DNA-binding activity in normal human monocytes, that the activation is rapid and persistent, and that the heavy ion-induced activation of NF-kappa B is mediated through phosphorylation of I-kappa B alpha and the subsequent proteasome-dependent degradation pathway. Since activation of NF-kappa B by extracellular stimuli is implicated in inflammation, infection and cancer induction, as well as in protection of cells against insult, it will be important in subsequent studies to elucidate whether heavy ion-induced NF-kappa B activation is involved in downstream gene expression.
Authors:
Mohan Natarajan; N Aravindan; M L Meltz; T S Herman
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Radiation and environmental biophysics     Volume:  41     ISSN:  0301-634X     ISO Abbreviation:  Radiat Environ Biophys     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-08-30     Completed Date:  2003-04-02     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0415677     Medline TA:  Radiat Environ Biophys     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  139-44     Citation Subset:  IM; S    
Affiliation:
Department of Radiation Oncology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. natarajan@uthscsa.edu
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MeSH Terms
Descriptor/Qualifier:
Cell Line
DNA / metabolism,  radiation effects
DNA-Binding Proteins / metabolism,  radiation effects
Dose-Response Relationship, Radiation
Gene Expression Regulation / radiation effects
Heavy Ions
Humans
I-kappa B Proteins / metabolism,  radiation effects*
Iron Radioisotopes / pharmacology*
Monocytes / metabolism*,  radiation effects*
NF-kappa B / metabolism*,  radiation effects*
Radiation, Ionizing
Reference Values
Sensitivity and Specificity
Signal Transduction
Transcription, Genetic / radiation effects*
Transcriptional Activation / radiation effects
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/I-kappa B Proteins; 0/Iron Radioisotopes; 0/NF-kappa B; 9007-49-2/DNA

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