NADPH oxidase of chondrocytes contains an isoform of the gp91phox subunit

Moulton, J. Paul; Goldring, B.; Hancock, T. John

doi:10.1042/bj3290449

Cited by 41 publications

(23 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have suggested that the nonphagocytic low-output NAD(P)H oxidase, occurring in most cell types, is an isoform of the phagocytic high-output enzyme (23). Differences have been found in the amino acid sequence of gp91phox (24), the polymorphism of the p22phox gene (25), and the involvement of Rac1 or Rac2 in the regulation of the high-and low-output NAD(P)H oxidase (26). These differences may explain how the production of erythropoietin in B cells of chronic granulomatous patients, who suffer from mutations in the phagocytic cytochrome b 558 , can be induced by hypoxia (27).…”

Section: Discussionmentioning

confidence: 98%

Chemoreceptor discharges and cytochrome redox changes of the rat carotid body: Role of heme ligands

Lahiri

Ehleben

Acker

1999

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In superfused in vitro rat carotid body, we recorded chemoreceptor discharges and the redox state of cytochromes simultaneously to identify the primary oxygensensing protein controlling transmitter release and electrical activity of the carotid sinus nerve. These parameters were tested under the inf luence of heme ligands such as oxygen, cyanide, 4-(2-aminoethyl)-benzenesulfonyl f luoride, and CO. During stimulation, there was an initial increase in discharge frequency followed by a decline or suppression of activity. Photometric changes lagged and were maintained as nerve activity decreased. Reducing mitochondrial cytochromes by cyanide or prolonged severe hypoxia, suppressed the chemoreceptor discharge. 4-(2-Aminoethyl)-benzenesulfonyl f luoride, a specific inhibitor of the phagocytic cytochrome b 558 , also silenced the chemoreceptors after an initial excitation. CO increased the chemoreceptor discharge under normoxia, an effect inhibited by light, when the cytochromes were not reduced. When the discharges were depressed by severe hypoxia, exposure to light excited the chemoreceptors and the cytochromes were reduced. The rapidity of the chemosensory responses to light and lack of effect on dopamine release from type I cells led us to hypothesize that carotid body type I cells and the apposed nerve endings use different mechanisms for oxygen sensing: the nerve endings generate action potentials in association with membrane heme proteins whereas cytosolic heme proteins signal the redox state, releasing modulators or transmitters from type I cells.

show abstract

Section: Discussionmentioning

confidence: 98%

Chemoreceptor discharges and cytochrome redox changes of the rat carotid body: Role of heme ligands

Lahiri

Ehleben

Acker

1999

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…14 Recently, components of phagocyte-type NADH/NADPH oxidases have been found in several nonphagocytic cell types, including fibroblasts, 42,43 VSM cells, 19,24 coronary endothelial cells, 11,12 renal mesangial cells, 44 chemoreceptor cells, 45 microglia, 46 and bone osteoclasts. 47 In these nonphagocytic cells, it is notable that ROS production is generally of relatively low magnitude and slow kinetics compared with the burstlike millimolar production of the activated neutrophil NADPH oxidase. Potential explanations for this difference could include the possibility that oxidase subunit structures (partic- ularly that of gp91-phox) and/or subunit expression level, stoichiometry, and location are different among the enzymes.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization and Localization of the NAD(P)H Oxidase Components gp91- phox and p22- phox in Endothelial Cells

Bayraktutan

Blayney

Shah

2000

ATVB

219

150

View full text Add to dashboard Cite

Abstract-The production of reactive oxygen species (ROS) within endothelial cells may have several effects, including alterations in the activity of paracrine factors, gene expression, apoptosis, and cellular injury. Recent studies indicate that a phagocyte-type NAD(P)H oxidase is a major source of endothelial ROS. In contrast to the high-output phagocytic oxidase, the endothelial enzyme has much lower biochemical activity and a different substrate specificity (NADHϾNADPH). In the present study, we (1) cloned and characterized the cDNA and predicted amino acid structures of the 2 major subunits of rat coronary microvascular endothelial cell NAD(P)H oxidase, gp91-phox and p22-phox; (2) undertook a detailed comparison with phagocytic NADPH oxidase sequences; and (3) studied the subcellular location of these subunits in endothelial cells. Although these studies revealed an overall high degree of homology (Ͼ90%) between the endothelial and phagocytic oxidase subunits, the endothelial gp91-phox sequence has potentially important differences in a putative NADPH-binding domain and in putative glycosylation sites. In addition, the subcellular location of the endothelial gp91-phox and p22-phox subunits is significantly different from that reported for the neutrophil oxidase, in that they are predominantly intracellular and collocated in the vicinity of the endoplasmic reticulum. This first detailed characterization of gp91-phox and p22-phox structure and location in endothelial cells provides new data that may account, in part, for the differences in function between the phagocytic and endothelial NAD(P)H oxidases. (Arterioscler Thromb Vasc

show abstract

“…In addition, the system produces nontoxic amounts of H 2 O 2 , consistent with its potential role in signaling by hormones, growth factors, and cytokines. Despite these differences, human fat cell plasma membranes contain a spectrally detectable cytochrome b 558 (4), suggesting that some of the components of human fat cell oxidase may be similar or identical to those of phagocyte oxidase, as has also been proposed for stimulus-sensitive redox activities of other non-phagocytic cells such as endothelia (29), fibroblasts (30,31), mesangial cells (32), chondrocytes (33), vascular smooth muscle cells (34 -36), and adventitial cells (37).…”

Section: G Protein ␤␥-Subunits Mediating the ␤-Adrenergic Inhibition mentioning

confidence: 99%

Inhibitory Effect of Isoproterenol on NADPH-dependent H2O2 Generation in Human Adipocyte Plasma Membranes Is Mediated by βγ-Subunits Derived from Gs

Krieger-Brauer¹,

Medda²,

Sattel³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

Previous studies revealed that human fat cell plasma membranes contain a multireceptor-linked H 2 O 2 -generating system that is under antagonistic control by hormones and cytokines and is stimulated by insulin via G␣ i2 . In this report, it is shown that the inhibitory action of the ␤-adrenergic agonist isoproterenol is mediated by G protein ␤␥-subunits, based on observations that its action was specifically reversed by anti-G␤ antibodies or a C-terminal ␤-adrenergic receptor kinase-1 fragment containing the G␤␥-binding site of the enzyme, and was mimicked by exogenously supplied G protein ␤␥-sub- There is growing evidence that redox-active biomolecules play important roles in signaling by hormones and cytokines (1-3). Ligand-induced changes in cellular redox status modulate tyrosine phosphorylation-dependent pathways of signal transduction; alter DNA binding and transactivation activities of many transcriptional activators; and may influence key steps in the synthesis, degradation, and action of cAMP and cGMP as well (2, 3). Previous work showed that human fat cells possess a plasma membrane-bound H 2 O 2 -generating system that is under antagonistic control by a large and diverse group of hormones and cytokines, including insulin, the ␤-adrenergic agonist isoproterenol, and different isoforms of fibroblast and platelet-derived growth factors (4 -7). The mechanisms by which hormones and cytokines regulated NADPH-dependent H 2 O 2 generation were confined to the plasma membrane, operated in the absence of ATP, and were independent of soluble second messengers, indicating that established pathways of signal transduction were not involved. These findings placed human fat cell oxidase in a position comparable with adenylyl cyclase and suggested a physical interaction between receptors and NADPH oxidase or receptor-effector coupling via signaltransducing protein(s). Indeed, recent work revealed that the stimulatory effect of insulin on NADPH-dependent H 2 O 2 generation is transduced via G␣ i2 (7).In this study, we have investigated whether the effects of the ␤-adrenergic agonist isoproterenol are also mediated by heterotrimeric G protein(s). Using specific antibodies against the ␣-and ␤-subunits of heterotrimeric G proteins and a peptide that specifically binds G␤␥, it is shown that the inhibitory effects of isoproterenol on NADPH-dependent H 2 O 2 generation are mediated by ␤␥-subunits. Taking advantage of the unique properties of a commercially available antibody directed against residues 100 -119 within the ␣-helical domain of G␣ s (K-20) and of the peptide corresponding to its target sequence, which are summarized in a recent publication (8), it is shown that the ␤␥-subunits mediating the inhibitory action of isoproterenol were derived from G s .

show abstract

NADPH oxidase of chondrocytes contains an isoform of the gp91phox subunit

Cited by 41 publications

References 17 publications

Chemoreceptor discharges and cytochrome redox changes of the rat carotid body: Role of heme ligands

Chemoreceptor discharges and cytochrome redox changes of the rat carotid body: Role of heme ligands

Molecular Characterization and Localization of the NAD(P)H Oxidase Components gp91- phox and p22- phox in Endothelial Cells

Inhibitory Effect of Isoproterenol on NADPH-dependent H2O2 Generation in Human Adipocyte Plasma Membranes Is Mediated by βγ-Subunits Derived from Gs

Contact Info

Product

Resources

About