This short review article summarizes what is known clinically and biochemically about the seven human NADPH oxidases. Emphasis is put on the connection between mutations in the catalytic and regulatory subunits of Nox2, the phagocyte defense enzyme, with syndromes like chronic granulomatous disease, as well as a number of chronic inflammatory diseases. These arise paradoxically from a lack of reactive oxygen species production needed as second messengers for immune regulation. Both Nox2 and the six other human NADPH oxidases display signaling functions in addition to the functions of these enzymes in specialized biochemical reactions, for instance, synthesis of the hormone thyroxine. NADPH oxidases are also needed by Saccharomyces cerevisiae cells for the regulation of the actin cytoskeleton in times of stress or developmental changes, such as pseudohyphae formation. The article shows that in certain cancer cells Nox4 is also involved in the re-structuring of the actin cytoskeleton, which is required for cell mobility and therefore for metastasis.

In diesem kurzen Übersichtsbeitrag fassen wir den klinischen und biochemischen Wissensstand zu den sieben menschlichen NADPH-Oxidasen zusammen. Ein Schwerpunkt liegt dabei auf dem Zusammenhang zwischen Mutationen in den katalytischen und regulatorischen Untereinheiten von Nox2 – der NADPH-Oxidase der Phagozyten mit Abwehrfunktion – und Syndromen wie der septischen Granulomatose, aber auch einer Reihe von chronisch-entzündlichen Erkrankungen. Hervorgerufen werden diese durch einen Mangel an reaktiven Sauerstoffspezies, welche als Produkte der NADPH-Oxidase-Reaktion für die Immunregulation notwendig sind. Sowohl Nox2 als auch die anderen sechs menschlichen NADPH-Oxidasen haben neben ihren Funktionen in spezialisierten biochemischen Reaktionen (Beispiel: Thyroxinsynthese) auch eine Funktion in der Signaltransduktion. In der Hefe Saccharomyces cerevisiae wird die NADPH-Oxidase Yno1 als Signalgeber für die Restrukturierung des Aktinzytoskeletts gebraucht, z. B. unter Stress oder bei der Bildung von Pseudohyphen. In bestimmten Tumorzellen ist die NADPH-Oxidase Nox4 ebenfalls an der Restrukturierung des Aktinzytoskeletts beteiligt – eine Voraussetzung für die Zellmobilität und damit auch für die Metastasierung dieser Tumoren.

Department of Biological Sciences University at Buffalo The State University of New York Buffalo USA

Department of Bioscienes University of Salzburg Salzburg Austria

Laboratory of Cell Reproduction Institute of Microbiology of AS CR v v i Prague Czech Republic

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