Cited by 147NF-κB Signaling PathwaysRedox biology and oxidative stressAldose Reductase and Taurine

Oxidation of IκBα at Methionine 45 Is One Cause of Taurine Chloramine-induced Inhibition of NF-κB Activation

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Kanayama, Atsuhiro, Inoue, Jun-ichiro, Sugita-Konishi, Yoshioko, Shimizu, Makoto, Miyamoto, Yusei·2002·Journal of Biological Chemistry

Abstract

A band shift of IkappaBalpha was observed in Western blots with Jurkat cells treated with 1 mm taurine chloramine (TauCl) for 1 h. TauCl treatment inhibited tumor necrosis factor alpha (TNFalpha)-initiated nuclear factor kappaB (NF-kappaB) activation. TauCl did not inhibit either the upstream of IkappaB kinase (IKK) activation or IKK itself but did inhibit NF-kappaB activation induced by IKK overexpression. Deletion experiments showed that a TauCl modification site causing the band shift of IkappaBalpha is Met45. High performance liquid chromatography and mass spectrometry analyses of a small peptide containing Met45 revealed that TauCl oxidizes Met45. A mutant of IkappaBalpha whose Met45 was converted to alanine did not generate a band shift upon TauCl treatment and degraded in response to TNFalpha stimulation. However, a reporter assay revealed that NF-kappaB-dependent luciferase expression was not fully recovered in cells transfected with this mutant. These results indicate that Met45 oxidation of IkappaBalpha is a molecular mechanism underlying the TauCl-induced inhibition of NF-kappaB activation. A similar band shift was observed when HL-60 cells expressing myeloperoxidase were treated with 100 microm hydrogen peroxide for 5 min. When rat neutrophils were incubated with bacteria, intracellular taurine decreased interleukin-8 production. Therefore, taurine may help suppress excessive inflammatory reaction in neutrophils.

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Authors
Kanayama, A., Inoue, J.-I., Sugita-Konishi, Y., Shimizu, M., & Miyamoto, Y.
Affiliations
  • The University of Tokyo (JP)
  • Keio University (JP)
  • National Institute of Infectious Diseases (JP)
Corresponding author
Miyamoto, Yusei
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-07
Volume
277
Issue
27
Pages
24049-24056
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2033761996
Cited by
147
References
35
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 2 · 2015: 10 · 2014: 3 · 2013: 6 · 2012: 6
FWCI
3.44
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
Keywords
taurine chloramine, IκBα, methionine oxidation, NF-κB activation, TNF signaling, IκB kinase, protein oxidation, myeloperoxidase, hydrogen peroxide, neutrophils, interleukin-8, inflammation reduction, Jurkat cells, HL-60 cells
MeSH terms
NF-KappaB Inhibitor alpha, Cell Line, Chromatography, High Pressure Liquid, DNA-Binding Proteins, Enzyme Inhibitors, Humans, Kinetics, Luciferases, Methionine, Oxidation-Reduction, Recombinant Proteins, Mass Spectrometry, Taurine, Oligonucleotide Probes, Interleukin-8, Mutagenesis, Site-Directed, NF-kappa B, Genes, Reporter, Jurkat Cells, Amino Acid Substitution, I-kappa B Proteins

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