Prominent publications by John T Curnutte

KOL Index score: 15451

Activation of the NADPH oxidase of phagocytic cells requires the action of Rac2 or Rac1, members of the Ras superfamily of GTP-binding proteins. Rac proteins are active when in the GTP-bound form and can be regulated by a variety of proteins that modulate the exchange of GDP for GTP and/or GTP hydrolysis. The p190 Rac GTPase Activating Protein (GAP) inhibits human neutrophil NADPH oxidase activity in a cell-free assay system with a K1 of approximately 100 nM. Inhibition by p190 was ...

Known for Rac Gtp |  Nadph Oxidase |  Activating Protein |  Phagocytic Cells |  Gap Activity
KOL Index score: 14778

We previously reported that granulocytes are able to produce superoxide (O(2) (-)), a highly reactive compound formed by the one-electron reduction of oxygen. The demonstration of O(2) (-) production was based on the observation that the reduction of extra-cellular cytochrome c by granulocytes was greatly diminished by superoxide dismutase, an enzyme catalyzing the conversion of O(2) (-) to hydrogen peroxide and oxygen. In the present report, studies concerning the effect of bacteria and ...

Known for Cytochrome Reduction |  Superoxide Dismutase |  Bacteria Serum |  O2 Production |  Humans Leukocytes
KOL Index score: 14560

When the neutrophil NADPH oxidase is activated to generate superoxide, the cytosolic components, p47phox, p67phox, and the GTP-binding protein Rac, become stably associated with the plasma membrane. The translocation of p47phox and p67phox is dependent on the presence in the membrane of the flavocytochrome b558, itself composed of two subunits, gp91phox and p22phox. In this study we have quantitated Rac1 and Rac2 in human neutrophils and show that > 96% of the Rac protein is Rac2 and ...

Known for Flavocytochrome B558 |  Oxidase Components |  P47phox P67phox |  Translocation Rac2 |  Neutrophil Nadph
KOL Index score: 14485

Guanine and/or adenine nucleotides appear to be involved in the activation of the superoxide-generating NADPH oxidase of phagocytic cells. Their precise roles, however, are unclear, as much of the evidence for their involvement comes from experiments in which nucleotides have been added to complex systems already rich in both endogenous nucleotides and enzymes capable of interconverting them. To circumvent this problem we have examined the role of nucleotides in neutrophil NADPH oxidase ...

Known for Oxidase Activation |  Atp Gtp |  Neutrophil Nadph |  Absolute Requirement |  Guanine Nucleotides
KOL Index score: 13129

The respiratory burst oxidase of neutrophils can be activated in a cell-free system in which solubilized membranes, cytosol, and Mg2+ are required and in which sodium dodecyl sulfate is used to convert the dormant oxidase to an active form. The 2',3'-dialdehyde analog of NADPH was used as an affinity label for the cytosolic NADPH binding component of the respiratory burst oxidase from human neutrophils. When treated with this affinity label in the presence of sodium cyanoborohydride to ...

Known for Respiratory Burst Oxidase |  Human Neutrophils |  Nadph Binding |  Affinity Label |  Treated Cytosol
KOL Index score: 13005

Two of the cytosolic NADPH oxidase components, p47-phox and p67-phox, translocate to the plasma membrane in normal neutrophils stimulated with phorbol myristate acetate (PMA). We have now studied the translocation process in neutrophils of patients with chronic granulomatous disease (CGD), an inherited syndrome in which the oxidase system fails to produce superoxide due to lesions affecting any one of its four known components: the gp91-phox and p22-phox subunits of cytochrome b558 (the ...

Known for Cytochrome B558 |  P67phox P47phox |  Chronic Humans Nadh |  Nadph Oxidoreductases |  Oxidase Assembly
KOL Index score: 12956

A membrane-bound cytochrome b, a heterodimer formed by a 91-kD glycoprotein (heavy chain) and a 22-kD polypeptide (light chain), is an essential component of the phagocyte NADPH-oxidase responsible for superoxide generation. Cytochrome b is absent in two subgroups of chronic granulomatous disease (CGD), an inherited disorder characterized by the lack of oxidase activity. Mutations in the cytochrome heavy chain gene, encoded by the CYBB locus in Xp21.1, result in the X-linked form of CGD. ...

Known for Chronic Granulomatous |  Gene Structure |  Light Chain |  Autosomal Recessive |  Human Pair
KOL Index score: 12461

A transgenic mouse strain that expresses the hepatitis B virus (HBV) large envelope protein in the liver was used to determine the extent of oxidative DNA damage that occurs during chronic HBV infection. This mouse strain develops a chronic necroinflammatory liver disease that mimics the inflammation, cellular hyperplasia, and increased risk for cancer that is evident in human chronic active hepatitis. When perfused in situ with nitroblue tetrazolium, an indicator for superoxide ...

Known for Transgenic Mice |  Hepatocellular Carcinoma |  Oxidative Dna Damage |  Liver Neoplasms |  Hepatitis Chronic
KOL Index score: 12130

Human neutrophils and other phagocytes generate superoxide anion (O2-) as a means of destroying ingested microorganisms. O2- is produced by an NADPH-consuming oxidase composed of membrane and cytosolic components. Activation of the NADPH oxidase is absolutely dependent upon GTP, indicating the requirement for a GTP-binding protein in this process. We have utilized a five-step chromatographic procedure to isolate a GTP-binding protein from human neutrophil cytosol which can stimulate ...

Known for Rac 2 |  Nadph Oxidase |  Binding Protein |  Human Neutrophil |  Affinity Chromatography
KOL Index score: 11901

The superoxide-generating enzyme of human neutrophils, NADPH oxidase, is converted from an inactive to an active form upon stimulation of the neutrophil. This activation process was examined using a recently developed cell-free system in which dormant oxidase is activated by arachidonic acid in the presence of a soluble factor from the neutrophil (Curnutte, J. T. (1985) J. Clin. Invest. 75, 1740-1743). NADPH oxidase from unstimulated human neutrophils was detected only in the membrane ...

Known for Nadph Oxidase |  Activation Process |  Membrane Fraction |  Cytosolic Factor |  Arachidonic Acid
KOL Index score: 11716

The respiratory burst oxidase of neutrophils can be activated in a cell-free system in which plasma membranes, cytosol, Mg2+, and a membrane-perturbing detergent, such as arachidonate or sodium dodecyl sulfate, are all required. Using the technique of preparative isoelectric focusing, the cytosol factor required for oxidase activation was resolved into four components termed C1-C4 with respective pI values of approximately 3.1, 6.0, 7.0, and 9.5. Individually, these components were ...

Known for Respiratory Burst Oxidase |  Cytosolic Components |  Granulomatous Disease |  Type Cgd |  Cellfree Cytosol
KOL Index score: 11613

The 47-kDa subunit of the NADPH oxidase system (p47-phox) of neutrophils undergoes an association with proteins in the Triton X-100-insoluble fraction upon stimulation of the cells with 4 beta-phorbol 12-myristate 13-acetate. This fraction contains the assembled oxidase that catalyzes the generation of superoxide by stimulated cells. In this paper, we report that the addition of an inhibitor of protein kinases (1-(5-isoquinolinylsulfonyl-2-methylpiperazine) to neutrophils that are ...

Known for Protein Kinase |  Phorbol Ester |  Superoxide Production |  P47phox Neutrophils |  Nadph Oxidase
KOL Index score: 11453

Rac1 and Rac2 are closely related, low molecular weight GTP-binding proteins that have both been implicated in regulation of phagocyte NADPH oxidase. This enzyme system is composed of multiple membrane-bound and cytosolic subunits and when activated catalyzes the one-electron reduction of oxygen to superoxide. Superoxide and its highly reactive derivatives are essential for killing microorganisms. Rac proteins undergo posttranslational processing, primarily the addition of an isoprenyl ...

Known for Rac Gtp |  Binding Proteins |  Nadph Oxidase |  Posttranslational Processing |  Human Neutrophil
KOL Index score: 11339

To combat bacterial infection, phagocytes generate superoxide (O2-) and other microbicidal oxygen radicals. NADPH oxidase, the enzyme responsible for O2- synthesis, is deficient in chronic granulomatous disease (CGD) patients. Although O2- generation is accompanied by a large burst of metabolic acid production, intracellular pH (pHi) remains near neutrality due to the concomitant stimulation of H+ extrusion. Three major pathways contribute to pHi regulation in activated phagocytes: ...

Known for Nadph Oxidase |  Activation Conductance |  Cgd Patients |  Conductive Pathway |  Dual Role


John T Curnutte: Influence Statistics

Sample of concepts for which John T Curnutte is among the top experts in the world.
Concept World rank
soluble stimuli consumption #1
deficiency p67 #1
chromosome publication cytochrome #1
129 cgd patients #1
activation reduced oxidase #1
superoxides cell #1
uncommon inherited disorder #1
nadph oxidoreductases drug #1
cells superoxide release #1
9 kindreds #1
selective decrease p67phox #1
deficient cytosol #1
phox superoxide #1
infections cgd patients #1
neutrophil superoxide nonidentical #1
pseudogene carries #1
nadph oxidase presence #1
normal oxidase exception #1
cytosol activate #1
staurosporine release #1
cgd arachidonic acid #1
mbl fcgammariia #1
x91 ∗ #1
granulocytes superoxide #1
recessive granulomatous #1
required oxidase #1
5 protein components #1
paha metabolite #1
neutrophils metabolism #1
cgd cytometric analysis #1
nadph oxidaseassociated fad #1
magnesium ion concentrations #1
413nm illumination #1
cgd component c4 #1
gtp nadph oxidoreductases #1
disease classification scheme #1
dic8 20 microm #1
failure superoxide #1
cellfree sonicates #1
low level nbt #1
phagocyte disorders consideration #1
p47phox fraction #1
rifngamma infections #1
regulate superoxide #1
superoxidegenerating enzyme #1
phox proteins data #1
p22phoxdeficiency #1
ruby kipnes #1
cytotoxic hydroxylamine #1

Key People For Chronic Granulomatous Disease

Top KOLs in the world
John I Gallin
chronic granulomatous disease membrane potential human neutrophils
Harry L Malech
chronic granulomatous disease gene therapy stem cells
John T Curnutte
chronic granulomatous disease nadph oxidase human neutrophils
Paul G Quie
polymorphonuclear leukocytes staphylococcus aureus chronic granulomatous disease
Stephen M Holland
chronic granulomatous disease gata2 deficiency nadph oxidase
Dirk Roos
chronic granulomatous disease human neutrophils respiratory burst

John T Curnutte:Expert Impact

Concepts for whichJohn T Curnuttehas direct influence:Chronic granulomatous disease,  Nadph oxidase,  Granulomatous disease,  Chronic granulomatous,  Human neutrophils,  Respiratory burst oxidase,  Respiratory burst,  Superoxide production.

John T Curnutte:KOL impact

Concepts related to the work of other authors for whichfor which John T Curnutte has influence:Nadph oxidase,  Chronic granulomatous disease,  Human neutrophils,  Oxidative stress,  Reactive oxygen species,  Respiratory burst,  Hydrogen peroxide.



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