Enzymic pathways involved in cell response to H2O2.
An influence of possible interaction of glutathione peroxidase and cyclooxygenase on the clonogenic survival of epithelial cells exposed in vitro to H2O2 was investigated. Indomethacin served as the inhibitor of cyclooxygenase, and the use of alkaline (7.5) or acidic (6.5) pH combined with controlled supply of glucose modified glutathione peroxidase activity. Indomethacin affected survival of cells exposed to H2O2 in a biphasic manner, enhancing cytotoxicity at lower hydrogen peroxide concentrations, and diminishing it at higher concentrations. The turning point moved gradually to higher concentrations of H2O2 corresponding to the augmented decomposition of hydrogen peroxide caused by increased activity of glutathione peroxidase. The data revealed that both enzymic pathways interact in the presence of H2O2, resulting in the overall cell survival different from that obtained after inhibition of either.
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Department of Chemical Pathology, University College and Middlesex School of Medicine, London, UK.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology*; D005947:Glucose / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D011451:Prostaglandin-Endoperoxide Synthases; D005947:Glucose; D007213:Indomethacin