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Papers In Press, published online ahead of print April 30, 2002
Integrated Biosciences, University of Tokyo, Kashiwa, Chiba 277-8562
Corresponding Author: yusei74{at}k.u-tokyo.ac.jp
A band shift of I kappa B alpha was observed in Western blots with Jurkat cells treated with 1 mM taurine chloramine (TauCl) for 1 hour. TauCl treatment inhibited TNF alpha-initiated NF kappa B activation. TauCl did not inhibit either the upstream of IKK activation or IKK itself but NF kappa B activation induced by IKK overexpression. Deletion experiments showed that a TauCl modification site causing the band shift of I kappa B alpha is the 45th methionine (Met45). HPLC and mass spectrometry analyses of a small peptide containing Met45 revealed that TauCl oxidizes Met45. A mutant of I kappa B alpha whose Met45 was converted to alanine did not generate a band shift upon TauCl treatment and degraded in response to TNF alpha stimulation. However, a reporter assay revealed that NF kappa B-dependent luciferase expression was not fully recovered in cells transfected with this mutant. These results indicate that Met45 oxidation of I kappa B alpha is a molecular mechanism underlying in TauCl-induced inhibition of NF kappa B 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.
J. Biol. Chem, 10.1074/jbc.M110832200
Submitted on November 12, 2001
Revised on April 30, 2002
Accepted on April 30, 2002
Oxidation of I
B
at Methionine 45 is one cause of taurine chloramine-induced inhibition of NF B activation
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