title: NADPH oxidases-do they play a role in TRPC regulation under hypoxia?
abstract: In the lung, acute alveolar hypoxia causes hypoxic pulmonary vasoconstriction (HPV) to maintain ventilation perfusion matching and thus optimal oxygenation of blood. In contrast, global chronic hypoxia triggers a pathological thickening of pulmonary arterial walls, called pulmonary vascular remodelling, leading to persistence of pulmonary hypertension (PH). Moreover, ischaemia or hypoxia can lead to a damage of pulmonary endothelial cells with subsequent oedema formation. Alterations in reactive oxygen species (ROS) have been suggested as a crucial mediator of such responses. Among the various sources of cellular ROS production, NADPH oxidases (NOXs) have been found to contribute to these physiological and pathophysiological signalling processes. NOXs are the only known examples that generate ROS as the primary function of the enzyme system. However, the downstream targets of NOX-derived ROS signalling in hypoxia are still not known. Canonical transient receptor potential (TRPC) channels recently have been recognised as directly or indirectly ROS-activated channels and have been shown to be essential for hypoxia-dependent vascular regulatory processes in the lung. Against this background, we here summarise the current knowledge on NOX-mediated TRPC channel signalling during hypoxia in the pulmonary circulation.
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardiopulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Aulweg 130, 35392, Giessen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Malczyk
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardiopulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Aulweg 130, 35392, Giessen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Veith
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardiopulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Aulweg 130, 35392, Giessen, Germany.
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Schermuly
authors.affiliation: Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians University Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gudermann
authors.affiliation: Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians University Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dietrich
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardiopulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Aulweg 130, 35392, Giessen, Germany.
authors.forename: Natascha
authors.initials: N
authors.lastname: Sommer
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardiopulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Aulweg 130, 35392, Giessen, Germany. Norbert.Weissmann@innere.med.uni-giessen.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardiopulmonary System (ECCPS), Member of the German Center for Lung Research (DZL), Aulweg 130, 35392, Giessen, Germany.
authors.forename: Oleg
authors.initials: O
authors.lastname: Pak
mesh_terms: D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D050052:TRPC Cation Channels; D019255:NADPH Oxidases
keywords: Hypoxic pulmonary vasoconstriction; NADPH oxidases; Pulmonary hypertension; Pulmonary vascular remodelling; Reactive oxygen species; Transient receptor potential channels