Hydrogen peroxide-induced apoptosis of HL-60 human leukemia cells is mediated by the oxidants hypochlorous acid and chloramines

Brett A. Wagner, Bradley E. Britigan, Krzysztof J. Reszka, Michael L. McCormick, C. Patrick Burns

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

We set out to identify whether HOCl, which is generated from H2O2/MPO/Cl-, is a proximal mediator of H2O2 programmed cell death in the HL-60 human leukemia cell. We found that authentic HOCl induces apoptosis in the HL-60 cell, Both the addition of methionine, an HOCl scavenger, and the removal of Cl- from the medium to prevent the formation of HOCl inhibited H2O2-induced apoptosis. HL-60 cells underwent apoptosis when exposed to HOCl in full medium, which gives rise to chloramines by the reaction of HOCl with amine groups, but not by HOCl in the amine-free HBSS, in which HOCl but not chloramines can be detected. Authentic chloramines induced apoptosis in this cell line in a concentration-dependent manner and at concentrations lower than HOCl. Full medium exposed to HOCl for 24 h would support methionine noninhibitable apoptosis, but did not react with 2-nitro-5-thiobenzoic acid (TNB), raising the possibility that the final inducer is a nonoxidant formed from HOCl and chloramines. We conclude that the signal for apoptosis induced by H2O2 in the MPO-containing HL-60 cell involves the reaction of the diffusible oxidant HOCl with amines producing chloramines and a subsequent non-TNB-reactive product.

Original languageEnglish (US)
Pages (from-to)223-234
Number of pages12
JournalArchives of Biochemistry and Biophysics
Volume401
Issue number2
DOIs
StatePublished - May 15 2002

    Fingerprint

Keywords

  • Aldehydes
  • Apoptosis
  • Chloramines
  • HL-60 cells
  • Hydrogen peroxide
  • Hypochlorous acid
  • Leukemia
  • Methionine Chloride

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this