Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human neutrophils, mastoparan induced rapid F-actin polymerization which was followed by a slow and sustained depolymerization to below the initial F-actin content. Incubation of neutrophils with pertussis toxin inhibited mastoparan-stimulated actin polymerization; however it did not prevent sustained depolymerization of F-actin. Analyses of phospholipids performed in parallel revealed that mastoparan stimulated rapid formation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and consumption of phosphatidylinositol 4,5-bisphosphate (PIP2). Pertussis toxin treatment blocked mastoparan-induced formation of PIP3. Furthermore, mastoparan stimulated the release of N-acetylglucosaminidase from primary granules. Cytochalasin B enhanced mastoparan-stimulated secretion. Mastoparan triggered superoxide radical production in a cytochalasin B-sensitive manner and induced complement type 3 receptor (CR3) up-regulation.
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PMID:Activation of human neutrophils by mastoparan. Reorganization of the cytoskeleton, formation of phosphatidylinositol 3,4,5-trisphosphate, secretion up-regulation of complement receptor type 3 and superoxide anion production are stimulated by mastoparan. 131 28

Botulinum C2 toxin, a binary toxin which selectively ADP-ribosylates nonmuscle G-actin, was used to evaluate the role of cytoskeletal rearrangement in ligand-evoked signal transduction and secretory processes in human neutrophils (polymorphonuclear leukocyte). Preincubation with the combined toxin components reduced the basal F-actin content and nearly completely suppressed the actin assembly initiated by the peptide and lipid chemoattractants formyl-methionyl-leucyl-phenylalanine, platelet activating factor, and leukotriene B4. Superoxide production and elastase secretion were increased markedly under these conditions. Concomitantly, ligand-elicited phosphoinositide hydrolysis was augmented with particular increase in inositol monophosphate. This was paralleled by a severalfold amplification of diacylglycerol formation and sustained elevation of cytosolic calcium. The toxin-effected amplification of postreceptor events and secretory responses was most pronounced in response to formyl-methionyl-leucyl-phenylalanine greater than platelet activating factor greater than leukotriene B4. All metabolic and secretory effects in C2 toxin-pretreated cells were sensitive to pertussis toxin inhibition. In conjunction with the recent finding of unchanged formyl-methionyl-leucyl-phenylalanine receptor binding and dissociation dynamics under influence of C2 (Norgauer, J., Just, I., Aktories, K., and Sklar, L. A. (1989) J. Cell Biol. 109, 1133-1140), the present investigation suggests amplification of postreceptor events as a major mechanism underlying C2 toxin-related increase in polymorphonuclear leukocyte secretory responses. Cytoskeletal rearrangement, putatively linked to phosphoinositide turnover and calcium transients, thus appears to be operative in temporal and/or spatial limitation of chemoattractant-evoked cellular signal transduction.
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PMID:Suppression of cytoskeletal rearrangement in activated human neutrophils by botulinum C2 toxin. Impact on cellular signal transduction. 165 81

Recombinant human granulocyte-colony stimulating factor (G-CSF) and recombinant human granulocyte/macrophage-colony stimulating factor (GM-CSF) stimulate neutrophil production from precursors in the marrow and enhance granulocyte functions in vitro. We studied the effects of G-CSF and GM-CSF on neutrophil superoxide production and secretion. G-CSF and GM-CSF alone stimulated neither superoxide production nor secretion, but both agents primed neutrophils for superoxide production stimulated by either N-formylmethionyl-leucyl-phenylalanine (FMLP) or ionomycin. Optimal priming occurred with G-CSF at 5.3 ng/ml for 20 minutes and for GM-CSF at 1 ng/ml for 60 minutes. Priming by GM-CSF was more readily inhibited by the tyrosine kinase inhibitor ST638 but was unaffected by staurosporine. Conversely, G-CSF priming was inhibited by staurosporine but not by ST638. Neither protein kinase C translocation nor increased protein kinase C activity, however, were observed after G-CSF/GM-CSF treatment. Priming by G-CSF and GM-CSF was sensitive to pertussis toxin, suggesting the involvement of guanine nucleotide-binding proteins (G-proteins). Neutrophils from three siblings with cyclic neutropenia were studied to observe the effects of G-CSF treatment on neutrophil function in vivo; sibling 1 and sibling 2 were treated with G-CSF for 6 months, but sibling 3 was not in the treatment group. Compared with neutrophils from normal donors, neutrophils from sibling 1 and sibling 2 were primed in vivo for superoxide release stimulated by either ionomycin or FMLP. Superoxide released by neutrophils from sibling 3 was similar to control cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant human G-CSF and GM-CSF prime human neutrophils for superoxide production through different signal transduction mechanisms. 172 Aug 2

A human polymorphonuclear leukocyte (PMN) activating factor (AFH-S) was isolated from a tropical plant seed, Aleurites Fordii Hemsl. (AFH) in PBS. It is found that the AFH-S stimulate human PMNs and induced superoxide generation and chemotaxis. Superoxide generation was affected by the extracellular calcium ion or pretreatment with H-7 (PK-C inhibitor), but not by mepacrine (PLA2 inhibitor) or pertussis toxin (islet-activating protein: IAP). Furthermore, a lag time exists dose-dependently. In addition the cytosolic calcium was not increased by the stimulation with AFH-S. Thus, the receptor for AFH-S was suggested to be independent from Ni-like protein, PI-response, or PLA2-activation, and stimulate PMNs through activation of PK-C.
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PMID:Human polymorphonuclear leukocyte activating factor isolated from Aleurites Fordii Hemsl. (Euphorbiaceae) seed. 285 81

In the chain of events by which chemotactic peptides stimulate NADPH oxidase-catalyzed superoxide formation in human neutrophils, the involvements of a pertussis toxin-sensitive guanine nucleotide-binding protein (N-protein), mobilization of intracellular calcium and protein kinase C stimulation have been proposed. Superoxide formation was studied in membranes from human neutrophils; NADPH oxidase was stimulated by arachidonic acid in the presence of neutrophil cytosol. Fluoride and stable GTP analogues, such as GTP gamma S and GppNHp, which all activate N-proteins, enhanced NADPH oxidase activity up to 4-fold. GDP beta S inhibited the effect of GTP gamma S. These data suggest that NADPH oxidase is regulated by an N-protein, independent of an elevation of the cytoplasmic calcium concentration.
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PMID:Guanine nucleotides stimulate NADPH oxidase in membranes of human neutrophils. 301 56

The role of G protein gamma subunit carboxylmethylation was examined in HL-60 granulocytes using an inhibitor of S-adenosylmethionine-dependent methylation, periodate-oxidized adenosine (Adox). A 40-60% reduction in gamma subunit carboxyl-methylation was associated with attenuation of fMet-Leu-Phe-stimulated GTP gamma S binding and GTP hydrolysis, while plasma membrane density of formyl peptide receptors, alpha i2, alpha i3, beta, gamma 5, and gamma 7 were not reduced. Reduced pertussis toxin-catalyzed ADP-ribosylation was re-established by in vitro methylation or addition of transducin beta gamma subunits. Superoxide release and inositol phosphate generation stimulated by fMet-Leu-Phe were significantly inhibited by Adox treatment. Carboxylmethylation contributes to transmembrane signalling and functional responses by enhancing association of alpha and beta gamma subunits.
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PMID:Role of carboxylmethylation in chemoattractant receptor-stimulated G protein activation and functional responses. 818 16

The effect of prostaglandin F2 alpha (PGF2 alpha) on superoxide radical production by macrophages was studied in pseudopregnant rats. Peritoneal macrophages prepared on day 7 or 13 of pseudopregnancy (psp) were incubated with various doses of PGF2 alpha for 90 min, and the production of superoxide radical was measured by the cytochrome C reduction method. PGF2 alpha significantly stimulated superoxide radical production by macrophages on day 13 of psp, but not on day 7 of psp. The pretreatment of macrophages with an inhibitor of protein kinase C (H7), Ca2+ channel blocker (Verapamil), Ca2+ chelators (EGTA, BAPTA), and an inhibitor of GTP-binding protein (pertussis toxin) prevented the stimulatory effects of PGF2 alpha on superoxide radical production. In conclusion, PGF2 alpha stimulated superoxide radical production by macrophages through the intracellular signal transduction pathway including activation of protein kinase C through the GTP-binding protein and Ca2+ influx, which would play important roles in the luteolytic process in psp rats.
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PMID:[Involvement of stimulatory effect of prostaglandin F2 alpha on superoxide radical production by macrophages in corpus luteum regression]. 875 99

Cultured human and rat endothelial cells were used to study cellular toxicity and Ca2+ signalling upon exposure to reactive oxygen species. Superoxide and hydrogen peroxide (O2.-/H2O2) were produced by the hypoxanthine/xanthine oxidase system (HX/XO) and caused intracellular Ca2+ concentration ([Ca2+]i) to rise steadily when activities above 2 mU/ml were used. These Ca2+ increases were also measured when the glucose/glucose oxidase (G/GO) system above 5 mU/ml was used to produce hydrogen peroxide (H2O2). Gross morphological changes appeared to parallel elevated [Ca2+]i levels preceding cell death. However, when HX/XO or G/GO were used at non toxic doses rapid and transient changes in [Ca2+]i were measured. These treatments did not alter subsequent receptor mediated Ca2+ signalling induced by ATP (10 microM) or histamine (100 microM). Superoxide dismutase (50 U/ml), which dismutates O2.- into H2O2 also had no influence, whereas catalase (50 U/ml), which removes H2O2, completely diminished transient [Ca2+]i responses. H2O2 added directly was able to induce similar Ca2+ transients when concentrations of at least 500 microM were used. Buffering trace amounts of iron (o-phenanthroline; 200 microM) in order to inhibit .OH radical formation was not effective to alter Ca2+ changes. Experiments performed in Ca(2+)-free buffer showed a similar rise in [Ca2+]i and readdition of Ca2+ to the extracellular medium indicated the activation of store operated Ca2+ entry. Blocking Ca(2+)-ATPases of the endoplasmatic reticulum with thapsigargin (1 microM) inhibited ROS induced transient increases and cells preincubated with pertussis toxin (200 nM) showed unchanged Ca2+ transients after exposure to both enzyme systems. Phospholipase C inhibitor U73122 (2 microM) effectively reduced hydrogen peroxide induced emptying of intracellular stores. Taken together, we demonstrate that enzymatically produced non-toxic H2O2 rather than O2.- or .OH causes calcium signalling from thapsigargin sensitive stores, and activates store operated Ca2+ entry at least partially by activating phospholipase C. These changes clearly differ from pathological 'oxidative stress' associated with a progressive increase in [Ca2+]i.
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PMID:Transient Ca2+ changes in endothelial cells induced by low doses of reactive oxygen species: role of hydrogen peroxide. 920 90

Amyloid beta protein (Abeta) alters signal transduction systems, including increases in the cytosolic free calcium ([Ca2+]i) response which have pathophysiological significance in Alzheimer's disease (AD). The purposes of this study were to elucidate the mechanism involved in Abeta's effect on the Ca2+ signal and to evaluate the effect of fullerenol-1, a water-soluble hydroxyl and superoxide radical scavenger, on the Abeta-induced Ca2+ response. Both Abeta and bradykinin (BK) dose-dependently elevated [Ca2+]i in PC12 cells. Fullerenol-1, at a concentration range between 100 nM and 1 microM, dose-dependently reduced the Abeta-induced [Ca2+]i response, but did not alter the subsequent BK-mediated process. Thapsigargin, an inhibitor of Ca2+-ATPase, released Ca2+ from the internal store and diminished the BK-mediated calcium spike but did not affect the Abeta-induced Ca2+ response. In the absence of extracellular calcium, the Abeta-induced, but not BK-induced, calcium spike was completely abolished. The Ca induced by Abeta did not enter through the voltage-dependent calcium channels or ligand gated calcium channels, because the peak of Abeta-evoked Ca2+ was not significantly altered by various Ca2+ channel blockers or a NMDA receptor antagonist MK801. In addition, neither cholera toxin nor pertussis toxin altered the Abeta-induced Ca response. The results demonstrated that Abeta-stimulated [Ca2+]i increase is due to Ca influx from an extracellular source rather than from the intracellular store. Alteration of the membrane lipid structure and permeability by free radicals generated by Abeta may be a major cause of Ca -influx. Furthermore, fullerenol-1, a novel antioxidant, may provide therapeutic benefits in neurodegenerative diseases such as AD.
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PMID:Blockage of amyloid beta peptide-induced cytosolic free calcium by fullerenol-1, carboxylate C60 in PC12 cells. 1079

Angiotensin II (Ang II) is able to induce free radical generation in neutrophils, which is more elevated in neutrophils of patients with hypercholesterolemia (HC). In addition, the signal processing through angiotensin I (Ang I) receptors is altered. In present study, we compared the Ang II-triggered free radical generation of neutrophils obtained from patients with relatively isolated forms of metabolic syndrome (MS) with membrane-bound cholesterol content and membrane fluidity. We determined the enhancement of Ang II-induced superoxide anion and leukotriene C(4) (LTC(4)) generation, membrane fluidity and cell-bound cholesterol content of neutrophils obtained from 12 control subjects, 11 patients with obesity (Ob), 10 patients with type 2 diabetes mellitus (t2-DM) and 12 patients with HC. The alteration of signal processing was studied after preincubation with different inhibiting drugs. Superoxide anion, LTC(4) production and membrane rigidity were increased in the following order: control < Ob < t2-DM < HC. Both Ang II-induced superoxide anion and LTC(4) generation were decreased in control cells by pertussis toxin and fluvastatin (Flu), whereas in each patient group, mepacrin, verapamil and Flu were effective, suggesting alterations in signal pathways, which may be attributed to isoprenylation. The enhancement of superoxide anion and LTC(4) generation correlated significantly with membrane rigidity, independently from the experimental groups and membrane-bound cholesterol content. Membrane rigidity of neutrophils, obtained from patients with MS, plays a role in Ang II-induced free radical generation independent of intracellular cholesterol homeostasis.
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PMID:The association between angiotensin II-induced free radical generation and membrane fluidity in neutrophils of patients with metabolic syndrome. 1754 12


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