Oxidation of IκBα at Methionine 45 Is One Cause of Taurine Chloramine-induced Inhibition of NF-κB Activation
Open accessAbstract
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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Negative modulation of NF-κB by N-chlorotaurine and other chloramines such as glycine chloramine is thought to originate from oxidation of Met45 in IκB, preventing its ubiquitination and proteasomal degradation.
“Negative modulation of NF-κB by N-chlorotaurine (and other chloramines such as glycine chloramine) is thought to originate from oxidation of Met45 in IκB (preventing its ubiquitination and proteasomal degradation) (116, 117).”
From Hypochlorous Acid: From Innate Immune Factor and Environmental Toxicant to Chemopreventive Agent Targeting Solar UV-Induced Skin Cancer (2022) · cites this paper as [117]
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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
- hybrid
- doi.org
- Licence
- 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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