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NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential
The discovery, biochemistry, pharmacology and clinical potential of haem-dependent sGC stimulators andHaem-independent sGC activators are reviewed. Expand
Hypoxia-Dependent Regulation of Nonphagocytic NADPH Oxidase Subunit NOX4 in the Pulmonary Vasculature
An important role for NOX4 in the vascular remodeling associated with development of pulmonary hypertension is supported by results supported by screening lung tissue for the expression of NADPH oxidase subunits. Expand
Direct Interaction of the Novel Nox Proteins with p22phox Is Required for the Formation of a Functionally Active NADPH Oxidase*
Evidence is provided that p22phox directly interacts with Nox1 and Nox4, to form an superoxide-generating NADPH oxidase and it is demonstrated that mutation of the potential heme binding site in the Nox proteins disrupts the complex formation of Nox 1 and NOx4 with p 22phox. Expand
Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement.
Whether novel NOX inhibitors enable reliable validation of NOX isoforms' pathological roles and whether this knowledge supports translation into pharmacological applications is discussed. Expand
Apocynin Is Not an Inhibitor of Vascular NADPH Oxidases but an Antioxidant
Observations indicate that apocynin predominantly acts as an antioxidant in endothelial cells and vascular smooth muscle cells and should not be used as an NADPH oxidase inhibitor in vascular systems. Expand
The NOX toolbox: validating the role of NADPH oxidases in physiology and disease
A critical review of the currently available experimental tools to assess the role of NOX and especially NOX4 is provided, and the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo is focused on, its specificity, selectivity, and possible mechanism of action. Expand
The nitric oxide and cGMP signal transduction system: regulation and mechanism of action.
Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels.
It is shown in vivo that oxidative stress and related vascular disease states, including human diabetes mellitus, led to an sGC that was indistinguishable from the in vitro oxidized/heme-free enzyme, and BAY 58-2667 was more effective and potentiated under pathophysiological and oxidative stress conditions. Expand
Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production.
The data suggest that Nox4 is responsible for basal H2O2 production, while O2*- production in nonstimulated and AngII-stimulated cells depends on Nox1, and the difference in the products generated by Nox 1 and Nox 4 may help to explain the distinct roles of these NADPH oxidases in cell signaling. Expand
Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration
The identification of NOX4 as a major source of oxidative stress in stroke and demonstration of dramatic protection after stroke in mice by NOX4 deletion or NOX inhibition, opens up new avenues forExpand