Intercellular HOCl-mediated Apoptosis Induction in Malignant Cells: Interplay Between NOX1-Dependent Superoxide Anion Generation and DUOX-related HOCl-generating Peroxidase Activity.
Intercellular apoptosis-inducing HOCl signaling is discussed as a control step during oncogenesis. It is defined as a sophisticated interplay between transformed target cells and non-transformed or transformed effector cells. In this study, transformed target cells were seeded as clumps of high local cell density, but low total cell number. They were surrounded by large numbers of effector cells, seeded at low local density. This spatially defined experimental arrangement allowed study of the impact of siRNA-mediated knockdown of NADPH oxidase 1 (NOX1) or dual oxidase 1 (DUOX1) on intercellular HOCl signaling. Our data show that the target function of transformed cells is defined as expression of NOX1 and subsequent extracellular superoxide anion generation. The NOX domain of DUOX1 does not contribute to the target function. The peroxidase domain of DUOX1 is released from transforming growth factor β1-treated non-transformed and transformed cells and acts in trans as HOCl-synthesizing peroxidase. These findings clarify the biochemical source of HOCl during HOCl-mediated signaling.
Department of Medical Microbiology and Hygiene, Institute of Virology, University of Freiburg, Freiburg, Germany.
Stefanie J
SJ
Pottgiesser
Department of Medical Microbiology and Hygiene, Institute of Virology, University of Freiburg, Freiburg, Germany.
Sonja
S
Heinzelmann
Department of Medical Microbiology and Hygiene, Institute of Virology, 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; D000074623:Dual Oxidases; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006997:Hypochlorous Acid / 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; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism*; 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
D016877:Oxidants; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D013481:Superoxides; 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; C524752:Duox1 protein, rat
Apoptosis; DUOX; HOCl; NOX1; hydroxyl radical; superoxide anion