Site-specific Effects of DUOX1-Related Peroxidase on Intercellular Apoptosis Signaling.
Intercellular apoptosis-inducing HOCl signaling is known as an interplay between superoxide anions/H₂O₂ of transformed target cells and dual oxidase 1 (DUOX1)-related peroxidase that is released from neighboring non-transformed or transformed effector cells. Effector cells are dispensable when the release of the peroxidase domain of DUOX1 from target cells is prevented through inhibition of matrix metalloproteinase (MMP) activity. Membrane-associated peroxidase is then co-localized to NADPH oxidase 1 (NOX1) and establishes HOCl signaling specifically in transformed cells, using the same biochemical pathways as classical intercellular HOCl signaling. Membrane-associated peroxidase protects against exogenous HOCl through reversal of the peroxidase reaction. In addition, membrane-associated peroxidase protects against NO/peroxynitrite signaling as it oxidates NO and decomposes peroxynitrite. The protective function of membrane-associated peroxidase (in the absence of MMP) is analogous to that of catalase, whereas the destructive effect of the enzyme, i.e. the synthesis of HOCl, is independent of its localization and of MMP activity.
Institute of Virology, Department of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany.
Sonja
S
Heinzelmann
Institute of Virology, Department of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany georg.bauer@uniklinik-freiburg.de.
Georg
G
Bauer
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology; D000074623:Dual Oxidases; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D016877:Oxidants; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006997:Hypochlorous Acid; D000074623:Dual Oxidases; D009195:Peroxidase; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C000614712:NOX1 protein, rat; C431513:DUOX1 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
DUOX1; HOCl; NOX1; apoptosis; matrix metalloproteinase