Abstract <p>This review has considered the mechanisms of intracellular and intercellular signaling regulation by myeloperoxidase (MPO), an enzyme in neutrophil azurophilic granules, during oxidative/halogenative stress and inflammation development. The stages of enzyme functioning and the formation of reactive halogen species are described. The functioning of MPO and production of reactive halogen species are shown to depend on the activity of NADPH oxidase; the role of NADPH oxidase and reactive oxygen species in the regulation of MPO function is discussed. Particular attention is focused on the role of biological molecules modified by reactive halogen species in modulating NADPH oxidase activity, exocytosis of granular proteins, NETosis, and other neutrophil functions, based on the principle of positive feedback. A special feature of the review is the discussion of the non-canonical function of MPO, namely its signaling role in the regulation of cellular processes, which is not associated with the catalytic activity of the enzyme.</p>

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Myeloperoxidase as a Regulator of Cell Signaling under Oxidative/Halogenative Stress

  • Irina V. Gorudko,
  • Daria V. Grigorieva,
  • Veronika E. Reut,
  • Grigory G. Martinovich,
  • Alexey V. Sokolov,
  • Oleg M. Panasenko

摘要

Abstract

This review has considered the mechanisms of intracellular and intercellular signaling regulation by myeloperoxidase (MPO), an enzyme in neutrophil azurophilic granules, during oxidative/halogenative stress and inflammation development. The stages of enzyme functioning and the formation of reactive halogen species are described. The functioning of MPO and production of reactive halogen species are shown to depend on the activity of NADPH oxidase; the role of NADPH oxidase and reactive oxygen species in the regulation of MPO function is discussed. Particular attention is focused on the role of biological molecules modified by reactive halogen species in modulating NADPH oxidase activity, exocytosis of granular proteins, NETosis, and other neutrophil functions, based on the principle of positive feedback. A special feature of the review is the discussion of the non-canonical function of MPO, namely its signaling role in the regulation of cellular processes, which is not associated with the catalytic activity of the enzyme.