Role of thiocyanate, bromide and hypobromous acid in hydrogen peroxide-induced apoptosis

Brett A. Wagner, Krzystof J. Reszka, Michael L. McCormick, Bradley E. Britigan, Crystal B. Evig, C. Patrick Burns

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

We have previously reported that H2O2-induced apoptosis in HL-60 human leukemia cells takes place in the presence of chloride, requires myeloperoxidase (MPO), and occurs through oxidative reactions involving hypochlorous acid and chloramines. We now report that when chloride is replaced by the pseudohalide thiocyanate, there is little or no H2O2-induced apoptosis. Furthermore, thiocyanate inhibits H2O2-induced apoptosis when chloride is present at physiological concentrations, and this occurs at thiocyanate concentrations that are present in human serum and saliva. In contrast, bromide can substitute for chloride in H2O2-induced apoptosis, but results in a lower percent of the cells induced into apoptosis. Hypobromous acid is likely a short-lived intermediate in this H2O2/MPO/bromide apoptosis, and reagent hypobromous acid and bromamines induce apoptosis in HL-60 cells. We conclude that the physiologic concentrations of thiocyanate found in human plasma could modulate the cytototoxicity of H2O2 and its resulting highly toxic MPO-generated hypochlorous acid by competing with chloride for MPO. Furthermore, the oxidative products of the reaction of thiocyanate with MPO are relatively innocuous for human leukemic cells in culture. In contrast, bromide can support H'2O2/MPO/halide apoptosis, but is less potent than chloride and it has no effect in the presence of physiological levels of chloride.

Original languageEnglish (US)
Pages (from-to)167-175
Number of pages9
JournalFree Radical Research
Volume38
Issue number2
DOIs
StatePublished - Feb 1 2004

Fingerprint

Bromides
Hydrogen Peroxide
Chlorides
Apoptosis
Peroxidase
Hypochlorous Acid
Chloramines
Plasma (human)
hypobromous acid
thiocyanate
Poisons
HL-60 Cells
Saliva
Leukemia
Cell Culture Techniques
Serum

Keywords

  • Apoptosis
  • Bromide
  • Hydrogen peroxide
  • Hypobromous acid
  • Myeloperoxidase
  • Thiocyanate

ASJC Scopus subject areas

  • Biochemistry

Cite this

Role of thiocyanate, bromide and hypobromous acid in hydrogen peroxide-induced apoptosis. / Wagner, Brett A.; Reszka, Krzystof J.; McCormick, Michael L.; Britigan, Bradley E.; Evig, Crystal B.; Burns, C. Patrick.

In: Free Radical Research, Vol. 38, No. 2, 01.02.2004, p. 167-175.

Research output: Contribution to journalReview article

Wagner, Brett A. ; Reszka, Krzystof J. ; McCormick, Michael L. ; Britigan, Bradley E. ; Evig, Crystal B. ; Burns, C. Patrick. / Role of thiocyanate, bromide and hypobromous acid in hydrogen peroxide-induced apoptosis. In: Free Radical Research. 2004 ; Vol. 38, No. 2. pp. 167-175.
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AU - McCormick, Michael L.

AU - Britigan, Bradley E.

AU - Evig, Crystal B.

AU - Burns, C. Patrick

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N2 - We have previously reported that H2O2-induced apoptosis in HL-60 human leukemia cells takes place in the presence of chloride, requires myeloperoxidase (MPO), and occurs through oxidative reactions involving hypochlorous acid and chloramines. We now report that when chloride is replaced by the pseudohalide thiocyanate, there is little or no H2O2-induced apoptosis. Furthermore, thiocyanate inhibits H2O2-induced apoptosis when chloride is present at physiological concentrations, and this occurs at thiocyanate concentrations that are present in human serum and saliva. In contrast, bromide can substitute for chloride in H2O2-induced apoptosis, but results in a lower percent of the cells induced into apoptosis. Hypobromous acid is likely a short-lived intermediate in this H2O2/MPO/bromide apoptosis, and reagent hypobromous acid and bromamines induce apoptosis in HL-60 cells. We conclude that the physiologic concentrations of thiocyanate found in human plasma could modulate the cytototoxicity of H2O2 and its resulting highly toxic MPO-generated hypochlorous acid by competing with chloride for MPO. Furthermore, the oxidative products of the reaction of thiocyanate with MPO are relatively innocuous for human leukemic cells in culture. In contrast, bromide can support H'2O2/MPO/halide apoptosis, but is less potent than chloride and it has no effect in the presence of physiological levels of chloride.

AB - We have previously reported that H2O2-induced apoptosis in HL-60 human leukemia cells takes place in the presence of chloride, requires myeloperoxidase (MPO), and occurs through oxidative reactions involving hypochlorous acid and chloramines. We now report that when chloride is replaced by the pseudohalide thiocyanate, there is little or no H2O2-induced apoptosis. Furthermore, thiocyanate inhibits H2O2-induced apoptosis when chloride is present at physiological concentrations, and this occurs at thiocyanate concentrations that are present in human serum and saliva. In contrast, bromide can substitute for chloride in H2O2-induced apoptosis, but results in a lower percent of the cells induced into apoptosis. Hypobromous acid is likely a short-lived intermediate in this H2O2/MPO/bromide apoptosis, and reagent hypobromous acid and bromamines induce apoptosis in HL-60 cells. We conclude that the physiologic concentrations of thiocyanate found in human plasma could modulate the cytototoxicity of H2O2 and its resulting highly toxic MPO-generated hypochlorous acid by competing with chloride for MPO. Furthermore, the oxidative products of the reaction of thiocyanate with MPO are relatively innocuous for human leukemic cells in culture. In contrast, bromide can support H'2O2/MPO/halide apoptosis, but is less potent than chloride and it has no effect in the presence of physiological levels of chloride.

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