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, Volume 36, Issue 1–2, pp 58–65 | Cite as

Biochemical mechanisms of hydrogen peroxide- and hypochlorous acid-mediated inhibition of human mononuclear leukocyte functionsin vitro: Protection and reversal by anti-oxidants

  • M. J. Smit
  • R. Anderson
Inflammation and Immunomodulation

Abstract

Both H2O2 (IC50=70 μM) and HOCl (IC50=8.5 μM) inhibited mitogen-induced MNL proliferation in a dose-dependent manner. This was found to be due to a depletion of intracellular ATP by at least two distinct mechanisms. HOCl and high concentrations (>100 μM) of H2O2 inhibit ATP generation via sulfhydryl group oxidation on the active site of the glyceraldehyde-3-phosphate dehydrogenase (G3PDH) enzyme of the glycolytic pathway. On the other hand, low H2O2 concentrations cause ATP depletion by an activation of the DNA repair enzyme, poly(ADP-ribose)polymerase (pADPRP), leading to consumption of NAD+, an essential cofactor for G3PDH. The anti-oxidants ascorbate and cysteine protected MNL against the anti-proliferative effects of HOCl. Similar results were achieved with the HOCl-mediated inhibition of ATP production and G3PDH activity. However, ascorbate was unable to protect against H2O2-mediated inhibition of MNL functions, while cysteine protected against the inhibitory effects on ATP production and G3PDH activity, induced by this oxidant.

Keywords

Sulfhydryl HOCl H2O2 Concentration Glycolytic Pathway Mononuclear Leukocyte 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag 1992

Authors and Affiliations

  • M. J. Smit
    • 1
  • R. Anderson
    • 2
  1. 1.MRC Unit for the Study of Phagocyte Function, Department of Immunology, Institute for Pathology, Faculty of MedicineUniversity of PretoriaRepublic of South Africa
  2. 2.Institute for PathologyPretoriaRepublic of South Africa

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