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

Abstract

We set out to identify whether HOCl, which is generated from H(2)O(2) /MPO/Cl(-), is a proximal mediator of H(2)O(2) 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 H(2)O(2)-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 H(2)O(2) 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.

• Authors: Brett A Wagner, Bradley E Britigan, Krzysztof J Reszka, Michael L McCormick, C Patrick Burns
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 401 Issue 2 Pg. 223-34 (May 15 2002) ISSN: 0003-9861 [Print] United States
• PMID: 12054473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
• Copyright: (c) 2002 Elsevier Science (USA).

Chemical References

• Chloramines
• Chlorides
• Culture Media
• Nitrobenzoates
• Oxidants
• Sulfhydryl Compounds
• thionitrobenzoic acid
• Hypochlorous Acid
• Methionine
• Hydrogen Peroxide

Topics

• Apoptosis (drug effects, physiology)
• Chloramines (metabolism)
• Chlorides (metabolism)
• Culture Media
• HL-60 Cells
• Humans
• Hydrogen Peroxide (pharmacology)
• Hypochlorous Acid (metabolism)
• Methionine (pharmacology)
• Models, Biological
• Necrosis
• Nitrobenzoates (metabolism)
• Oxidants (metabolism)
• Sulfhydryl Compounds