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

  • Inflammation and Immunomodulation
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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.

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Authors and Affiliations

  1. MRC Unit for the Study of Phagocyte Function, Department of Immunology, Institute for Pathology, Faculty of Medicine, University of Pretoria, Republic of South Africa

    M. J. Smit

  2. Institute for Pathology, PO Box 2034, 0001, Pretoria, Republic of South Africa

    R. Anderson

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  1. M. J. Smit
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  2. R. Anderson
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Smit, M.J., Anderson, R. Biochemical mechanisms of hydrogen peroxide- and hypochlorous acid-mediated inhibition of human mononuclear leukocyte functionsin vitro: Protection and reversal by anti-oxidants. Agents and Actions 36, 58–65 (1992). https://doi.org/10.1007/BF01991229

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  • DOI: https://doi.org/10.1007/BF01991229

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