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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


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.


Sulfhydryl HOCl H2O2 Concentration Glycolytic Pathway Mononuclear Leukocyte 
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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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