Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Am J Physiol Renal Physiol
2013 Oct 01;3057:F995-F1005. doi: 10.1152/ajprenal.00098.2013.
Show Gene links
Show Anatomy links
Fulvene-5 inhibition of Nadph oxidases attenuates activation of epithelial sodium channels in A6 distalnephron cells.
Trac D
,
Liu B
,
Pao AC
,
Thomas SV
,
Park M
,
Downs CA
,
Ma HP
,
Helms MN
.
???displayArticle.abstract???
Nadph oxidase 4 is an important cellular source of reactive oxygen species (ROS) generation in the kidney. Novel antioxidant drugs, such as Nox4 inhibitor compounds, are being developed. There is, however, very little experimental evidence for the biological role and regulation of Nadph oxidase isoforms in the kidney. Herein, we show that Fulvene-5 is an effective inhibitor of Nox-generated ROS and report the role of Nox isoforms in activating epithelial sodium channels (ENaC) in A6 distalnephron cells via oxidant signaling and cell stretch activation. Using single-channel patch-clamp analysis, we report that Fulvene-5 blocked the increase in ENaC activity that is typically observed with H2O2 treatment of A6 cells: average ENaC NPo values decreased from a baseline level of 1.04 ± 0.18 (means ± SE) to 0.25 ± 0.08 following Fulvene-5 treatment. H2O2 treatment failed to increase ENaC activity in the presence of Fulvene-5. Moreover, Fulvene-5 treatment of A6 cells blocked the osmotic cell stretch response of A6 cells, indicating that stretch activation of Nox-derived ROS plays an important role in ENaC regulation. Together, these findings indicate that Fulvene-5, and perhaps other classes of antioxidant inhibitors, may represent a novel class of compounds useful for the treatment of pathological disorders stemming from inappropriate ion channel activity, such as hypertension.
Agarwal,
Oxidative stress in hypertension and chronic kidney disease: role of angiotensin II.
2004, Pubmed
Agarwal,
Oxidative stress in hypertension and chronic kidney disease: role of angiotensin II.
2004,
Pubmed
Ago,
Pathophysiological roles of NADPH oxidase/nox family proteins in the vascular system. -Review and perspective-.
2011,
Pubmed
Alexander,
Theodore Cooper Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective.
1995,
Pubmed
Babior,
NADPH oxidase: an update.
1999,
Pubmed
Bedard,
The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology.
2007,
Pubmed
Bhandarkar,
Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice.
2009,
Pubmed
Block,
Subcellular localization of Nox4 and regulation in diabetes.
2009,
Pubmed
Borbély,
Small-molecule inhibitors of NADPH oxidase 4.
2010,
Pubmed
Brömme,
DCFH2 interactions with hydroxyl radicals and other oxidants--influence of organic solvents.
2008,
Pubmed
Caldiz,
Mineralocorticoid receptor activation is crucial in the signalling pathway leading to the Anrep effect.
2011,
Pubmed
Chabrashvili,
Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney.
2002,
Pubmed
Cross,
The NADPH oxidase of professional phagocytes--prototype of the NOX electron transport chain systems.
2004,
Pubmed
Cucoranu,
NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts.
2005,
Pubmed
El Jamali,
Regulation of phagocyte NADPH oxidase by hydrogen peroxide through a Ca(2+)/c-Abl signaling pathway.
2010,
Pubmed
El Jamali,
Novel redox-dependent regulation of NOX5 by the tyrosine kinase c-Abl.
2008,
Pubmed
Evans,
Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes.
2002,
Pubmed
Fink,
Detection of intracellular superoxide formation in endothelial cells and intact tissues using dihydroethidium and an HPLC-based assay.
2004,
Pubmed
Floyd,
Antioxidants, oxidative stress, and degenerative neurological disorders.
1999,
Pubmed
Forbes,
Oxidative stress as a major culprit in kidney disease in diabetes.
2008,
Pubmed
Geiszt,
The Nox family of NAD(P)H oxidases: host defense and beyond.
2004,
Pubmed
Geiszt,
Identification of renox, an NAD(P)H oxidase in kidney.
2000,
Pubmed
Gill,
NADPH oxidases in the kidney.
2006,
Pubmed
Goodson,
Nadph oxidase regulates alveolar epithelial sodium channel activity and lung fluid balance in vivo via O⁻₂ signaling.
2012,
Pubmed
Graham,
NADPH oxidase 4 is an oncoprotein localized to mitochondria.
2010,
Pubmed
Griendling,
Oxidative stress and cardiovascular injury: Part II: animal and human studies.
2003,
Pubmed
Haque,
Assessment of renal functional phenotype in mice lacking gp91PHOX subunit of NAD(P)H oxidase.
2004,
Pubmed
Harrison,
Oxidative stress and hypertension.
2009,
Pubmed
Haurani,
Nox4 oxidase overexpression specifically decreases endogenous Nox4 mRNA and inhibits angiotensin II-induced adventitial myofibroblast migration.
2008,
Pubmed
Helms,
Redox regulation of epithelial sodium channels examined in alveolar type 1 and 2 cells patch-clamped in lung slice tissue.
2008,
Pubmed
Heumüller,
Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant.
2008,
Pubmed
Ilatovskaya,
ROS production as a common mechanism of ENaC regulation by EGF, insulin, and IGF-1.
2013,
Pubmed
Jaquet,
Small-molecule NOX inhibitors: ROS-generating NADPH oxidases as therapeutic targets.
2009,
Pubmed
Koch,
Oxidative stress and antioxidant defenses in ethanol-induced cell injury.
2004,
Pubmed
Kourie,
Interaction of reactive oxygen species with ion transport mechanisms.
1998,
Pubmed
Kuroda,
NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart.
2010,
Pubmed
Lambeth,
NOX enzymes as novel targets for drug development.
2008,
Pubmed
Landmesser,
Role of p47(phox) in vascular oxidative stress and hypertension caused by angiotensin II.
2002,
Pubmed
Lee,
NOX4 as an oxygen sensor to regulate TASK-1 activity.
2006,
Pubmed
Li,
Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production.
1998,
Pubmed
Lyle,
Poldip2, a novel regulator of Nox4 and cytoskeletal integrity in vascular smooth muscle cells.
2009,
Pubmed
Ma,
Hydrogen peroxide stimulates the epithelial sodium channel through a phosphatidylinositide 3-kinase-dependent pathway.
2011,
Pubmed
,
Xenbase
Ma,
ATP masks stretch activation of epithelial sodium channels in A6 distal nephron cells.
2002,
Pubmed
Makino,
Increased renal medullary oxidative stress produces hypertension.
2002,
Pubmed
Martyn,
Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases.
2006,
Pubmed
Meng,
Insulin-like growth factor-I induces reactive oxygen species production and cell migration through Nox4 and Rac1 in vascular smooth muscle cells.
2008,
Pubmed
Menshikov,
Urokinase plasminogen activator stimulates vascular smooth muscle cell proliferation via redox-dependent pathways.
2006,
Pubmed
Minakami,
Phagocytosis-coupled activation of the superoxide-producing phagocyte oxidase, a member of the NADPH oxidase (nox) family.
2006,
Pubmed
Mochizuki,
Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells.
2006,
Pubmed
Modlinger,
RNA silencing in vivo reveals role of p22phox in rat angiotensin slow pressor response.
2006,
Pubmed
Montezano,
Oxidative stress, Noxs, and hypertension: experimental evidence and clinical controversies.
2012,
Pubmed
Murphy,
How mitochondria produce reactive oxygen species.
2009,
Pubmed
Oberg,
Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease.
2004,
Pubmed
Oeckler,
Stretch enhances contraction of bovine coronary arteries via an NAD(P)H oxidase-mediated activation of the extracellular signal-regulated kinase mitogen-activated protein kinase cascade.
2003,
Pubmed
Orient,
Novel sources of reactive oxygen species in the human body.
2007,
Pubmed
Paclet,
Localization of Nox2 N-terminus using polyclonal antipeptide antibodies.
2004,
Pubmed
Paravicini,
NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities.
2008,
Pubmed
Park,
Role of NADPH oxidase 4 in lipopolysaccharide-induced proinflammatory responses by human aortic endothelial cells.
2006,
Pubmed
Parkos,
Primary structure and unique expression of the 22-kilodalton light chain of human neutrophil cytochrome b.
1988,
Pubmed
Pendyala,
Role of Nox4 and Nox2 in hyperoxia-induced reactive oxygen species generation and migration of human lung endothelial cells.
2009,
Pubmed
Pullar,
Diphenyleneiodonium triggers the efflux of glutathione from cultured cells.
2002,
Pubmed
Rafii,
O2-induced ENaC expression is associated with NF-kappaB activation and blocked by superoxide scavenger.
1998,
Pubmed
Riganti,
Diphenyleneiodonium inhibits the cell redox metabolism and induces oxidative stress.
2004,
Pubmed
Ryu,
FcgammaRIIa mediates C-reactive protein-induced inflammatory responses of human vascular smooth muscle cells by activating NADPH oxidase 4.
2007,
Pubmed
Schröder,
Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase.
2012,
Pubmed
Serrander,
NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation.
2007,
Pubmed
Snyder,
Intoxicated Na(+) channels. Focus on "ethanol stimulates epithelial sodium channels by elevating reactive oxygen species".
2012,
Pubmed
Sourial,
Application of Dolichos biflorus in immunoassay detection of kidney collecting duct biomarkers.
2010,
Pubmed
Sturrock,
Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells.
2006,
Pubmed
Sun,
Angiotensin II stimulates epithelial sodium channels in the cortical collecting duct of the rat kidney.
2012,
Pubmed
Takemura,
Rac1-mediated NADPH oxidase release of O2- regulates epithelial sodium channel activity in the alveolar epithelium.
2010,
Pubmed
Touyz,
Apocynin, NADPH oxidase, and vascular cells: a complex matter.
2008,
Pubmed
Turrens,
Mitochondrial formation of reactive oxygen species.
2003,
Pubmed
Ushio-Fukai,
Compartmentalization of redox signaling through NADPH oxidase-derived ROS.
2009,
Pubmed
Vaziri,
Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats.
2000,
Pubmed
Vaziri,
Roles of oxidative stress and antioxidant therapy in chronic kidney disease and hypertension.
2004,
Pubmed
Vejrazka,
Apocynin inhibits NADPH oxidase in phagocytes but stimulates ROS production in non-phagocytic cells.
2005,
Pubmed
Vignais,
The superoxide-generating NADPH oxidase: structural aspects and activation mechanism.
2002,
Pubmed
Wallace,
Electrolyte and fluid secretion by cultured human inner medullary collecting duct cells.
2002,
Pubmed
Yu,
Aldosterone-induced increases in superoxide production counters nitric oxide inhibition of epithelial Na channel activity in A6 distal nephron cells.
2007,
Pubmed
,
Xenbase
Yu,
Single-channel analysis of functional epithelial sodium channel (ENaC) stability at the apical membrane of A6 distal kidney cells.
2008,
Pubmed
,
Xenbase