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)

The infiltration of neutrophils which phagocytose and kill microorganisms is an important defense mechanism against infections of the airways. Bordetella pertussis is a human respiratory pathogen which colonizes ciliated epithelium, causing whooping cough. We have investigated the effects of the peptidoglycan fragment tracheal cytotoxin (TCT) of B. pertussis on human neutrophil function in vitro. TCT (10(-6) to 10(-8) M) was toxic for human neutrophils, as measured by lactate dehydrogenase release and levels of intracellular ATP. TCT (10(-9) to 10(-15) M) did not stimulate neutrophil migration or chemiluminescence and did not affect neutrophil phagocytosis. Incubation of neutrophils for 20 min with TCT (10(-9) to 10(-11) M) significantly inhibited (P < 0.05) their subsequent migration toward the chemotactic factor N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 10(-9) M). Incubation of neutrophils for 20 min with TCT (10(-9) to 10(-15) M) significantly inhibited (P < 0.05) chemiluminescence stimulated by FMLP (10(-5) M). TCT (10(-6) to 10(-12) M) did not stimulate interleukin-1 alpha production by neutrophils or serum complement activation by the alternate pathway. We conclude that TCT at concentrations of < 10(-8) M affects important neutrophil functions and at higher concentrations is toxic. TCT may therefore contribute to the survival of B. pertussis within the airways in vivo.
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PMID:Effect of tracheal cytotoxin from Bordetella pertussis on human neutrophil function in vitro. 830 Feb 20

Mastoparan (5-30 microM), a tetradecapeptide isolated from wasp venom, caused histamine release from RBL-2H3 cells in a concentration- and time-dependent manner. Mastoparan-induced histamine release remained after removing the extracellular Ca2+, whereas the antigen-induced one disappeared. Pertussis toxin did not inhibit mastoparan-induced histamine release from the cells, and mastoparan did not stimulate phosphoinositide hydrolysis. In agreement with the results, RBL-2H3 cells had a small amount of ADP-ribosylation substrates for pertussis toxin. Neomycin (1-5 mM) suppressed mastoparan-induced histamine release and phospholipase D activation. However, butanol slightly inhibited mastoparan-induced histamine release. Moreover, 2,3-diphosphoglycerate inhibited mastoparan-induced phospholipase D activation, but not it's histamine release. On the other hand, mastoparan caused the leakage of lactate dehydrogenase from the cells in a similar concentration range to the histamine release. This leakage was also suppressed by neomycin. These results suggest that mastoparan enhances the membrane permeability, resulting in histamine release in a pertussis toxin-insensitive manner, and that mastoparan-induced phospholipase D activation may not relate to histamine release.
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PMID:Characterization of mastoparan-induced histamine release from RBL-2H3 cells. 963 64

1. Using an in vitro model of shear stress-induced cell injury we demonstrate that application of shear to differentiated human SH-SY5Y cells leads to cell death characterized by DNA fragmentation. Controlled shear stress was applied to cells via a modified cone and plate viscometer. 2. We show that pulsatile shear stress leads to DNA fragmentation, as determined via flow cytometry of fluorescein-12-dUTP nick-end labelled cells, in 45 +/- 4 % of cells. No lactate dehydrogenase (LDH) release was observed immediately after injury; however, 24 h after injury significant LDH release was observed. 3. Nitric oxide production by cells subjected to pulsatile shear increased two- to threefold over that in unsheared control cells. 4. Inhibition of protein synthesis, nitric oxide production, Ca2+ entry into cells, and pertussis toxin-sensitive G protein activation attenuated the shear stress-induced cell injury. 5. Our results show for the first time that application of pulsatile shear stress to a neuron-like cell in vitro leads to nitric oxide-dependent cell death.
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PMID:Pulsatile shear stress leads to DNA fragmentation in human SH-SY5Y neuroblastoma cell line. 1005 3

Oxidized low-density lipoproteins (oxLDL) have been shown to play a crucial role in atherosclerosis, but the underlying molecular mechanisms have not been fully understood. The present study showed that oxLDL strongly evoked phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) in rat vascular smooth muscle cells (VSMCs) in concentration- and time-dependent manners, reaching the maximal activation at 100 microg/mL within 5 minutes. The results from immunofluorescence staining also revealed that p38 MAPK was activated by oxLDL in 5 minutes, and the activated p38 MAPK was translocated from cytoplasm to nucleus of VSMCs in 15 minutes. Activation of p38 MAPK by oxLDL was apparently not mediated by their classical scavenger receptors and was not affected by tyrosine kinase inhibitors. However, activation of p38 MAPK was effectively blocked by pretreatment with pertussis toxin and was significantly reduced by phospholipase C inhibitor U-73122. OxLDL also inhibited forskolin-stimulated cAMP accumulation and increased inositol phosphate formation. More interestingly, inhibition of p38 MAPK by its specific inhibitor SB203580 significantly blocked oxLDL-induced cytotoxicity (increased leakage of cytoplasmic lactate dehydrogenase to the culture medium, reduced [3H]thymidine incorporation, and attenuated mitochondrial metabolism of tetrazolium salt, (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-s ulfophenyl)- 2H-tetrazolium), MTS) in VSMCs, and pretreatment with pertussis toxin also inhibited oxLDL-induced cytotoxicity. Taken together, our data clearly demonstrated that oxLDL effectively activated p38 MAPK in VSMCs, which was likely mediated via pertussis toxin-sensitive G proteins, and the p38 activation was functionally associated with oxLDL-induced cytotoxicity in VSMCs.
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PMID:Activation of p38 mitogen-activated protein kinase by oxidized LDL in vascular smooth muscle cells: mediation via pertussis toxin-sensitive G proteins and association with oxidized LDL-induced cytotoxicity. 1020 51

The present study was designed to clarify the mechanism of histamine release caused by levofloxacin, a fluoroquinolone antibacterial agent, using rat peritoneal mast cells. Levofloxacin induced a concentration-dependent histamine secretion from 300 microg/ml without lactate dehydrogenase leakage, and the release was rapidly completed within 30 s. This action was dependent on temperature, energy, pH and intracellular Ca(2+), similarly to the effect of compound 48/80, a basic compound. Unlike that with the calcium ionophore A23187, histamine secretion due to levofloxacin or compound 48/80 was prevented by pretreatment with either pertussis toxin or benzalkonium chloride, a selective inhibitor of G proteins of G(i) subtypes. Moreover, the histamine release elicited by levofloxacin or compound 48/80 was suppressed by hydrolysis of sialic acid residues on the cell surface brought about by neuraminidase. These results demonstrate that the mechanism by which levofloxacin exerts histamine release may be closely linked to activation of pertussis toxin-sensitive G proteins.
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PMID:Mechanism of histamine release induced by levofloxacin, a fluoroquinolone antibacterial agent. 1077 Oct 34

Mastoparan, a widely used tetradecapeptide activator of Gi/Go G proteins, has been reported to be a potent co-mitogen for Swiss 3T3 fibroblasts. However, we have previously shown that the peptide promotes the release of lactate dehydrogenase from Swiss 3T3 cells and evokes only a modest and delayed increase in DNA. We suggested that the ability of the peptide to permeabilise these cells may account for its mitogenic action. Here we show that mastoparan caused a rapid release of fluorescein from cells which had been pre-incubated with fluorescein diacetate, indicating that the peptide increases membrane permeability to small molecules. Furthermore, the release of lactate dehydrogenase evoked by mastoparan was lost after prolonged (24 h) incubation of cells with the peptide. Together, these data indicate that mastoparan-induced cell permeabilisation is both rapid and transient. We have also shown that mastoparan increased c-fos mRNA accumulation and that this response was not influenced by pertussis toxin or indomethacin. Although mastoparan increased the intracellular calcium concentration, the removal of extracellular calcium had no effect on mastoparan stimulated c-fos mRNA accumulation. These data show that mastoparan-induced c-fos mRNA accumulation is not mediated by activation of a G protein and subsequent activation of phospholipase D nor by a non-selective increase in calcium influx. The data have significance for the interpretation of studies in which mastoparan is, or has been, used as an activator of Gi/Go.
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PMID:Mastoparan transiently permeabilizes Swiss 3T3 cells and induces c-fos proto-oncogene expression. Role of calcium and G protein activation. 1078 31

Pasteurella (Mannheimia) haemolytica leukotoxin (Lkt) is the major factor that contributes to lung injury in bovine pneumonic pasteurellosis. Lkt is a pore-forming exotoxin that has the unique property of inducing cytolysis only in ruminant leukocytes and platelets. Cytolysis of many cell types is mediated by arachidonic acid (AA) and its generation by phospholipases is regulated by G-protein-coupled receptors. However, the contribution of Lkt-induced AA generation to cytolysis and the signalling cascade underlying AA generation in bovine leukocytes have not been determined. We have determined whether AA mediates Lkt-induced cytolysis and delineated the signalling mechanisms underlying AA generation in bovine leukocytes. Bovine lymphoma cells were used as an experimental system to investigate the Lkt-induced [(3)H] AA release, an index of AA generation and lactate dehydrogenase release, an index of cytolysis. The results indicate that Lkt induces AA release and cytolysis in a concentration- and time-dependent fashion. The AA analog, 5,8,11,14-eicosatetraynoic acid inhibited Lkt-induced cytolysis, but not AA release. Lkt-induced AA release and cytolysis were inhibited by pertussis toxin, inhibitors of cytosolic phospholipase A(2)(cPLA(2)), phospholipase C and protein kinase C (PKC), and by chelation of intracellular calcium. Furthermore, Western blot analysis revealed the presence of G(i), G(s)and G(q)type G-proteins. These results demonstrate that AA metabolites from cPLA(2)activation contribute to Lkt-induced cytolysis and G(i)type G-proteins, Ca(2+)and PKC, regulate the cPLA(2)activity.
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PMID:Pasteurella (Mannheimia) haemolytica leukotoxin-induced cytolysis of bovine leukocytes: role of arachidonic acid and its regulation. 1116 86

Alteration of [Ca2+]i by hyperglycemia is implicated in the pathogenesis of diabetic nephropathy. However, the effect of high glucose on Ca2+ regulation in proximal tubule cells is not known. Thus, we examined the mechanisms by which high glucose regulates Ca2+ uptake in primary cultured rabbit renal proximal tubule cells. Glucose increased the Ca2+ uptake in a time- and dose-dependent manner. A stimulatory effect of high glucose on Ca2+ uptake is predominantly observed using 25 mM glucose (high glucose) after 1 h, while 25 mM glucose did not affect cell viability and lactate dehydrogenase release. However, 25 mM mannitol and L-glucose did not affect Ca2+ uptake as compared with controls. Nifedipine and methoxyverapamil (L-type Ca2+ channel blockers) blocked high-glucose-induced stimulation of Ca2+ uptake. High-glucose-induced stimulation of Ca2+ uptake was blocked by pertussis toxin, SQ-22536 (adenylate cyclase inhibitor), myristoylated amide 14-22 (protein kinase A inhibitor), neomycin and U-73122 (phospholipase C inhibitors), and staurosporine and bisindolylmaleimide I (protein kinase C inhibitors). In addition, KN-62 (a Ca2+/calmodulin-dependent protein kinase II inhibitor) and W-7 (a Ca2+/calmodulin antagonist) blocked high-glucose-induced stimulation of Ca2+ uptake. In conclusion, high glucose stimulates the Ca2+ uptake through L-type Ca2+ channels via G-protein-coupled adenylate cyclase/cAMP and phospholipase C/protein kinase C pathways.
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PMID:High glucose stimulates Ca2+ uptake via cAMP and PLC/PKC pathways in primary cultured renal proximal tubule cells. 1117 1

We have recently demonstrated protection against renal ischemic-reperfusion injury in vivo by A(1)- and A(2a)-adenosine receptor (AR) modulations. To further elucidate the signaling cascades of AR-induced cytoprotection against reperfusion/oxidant-mediated injury, immortalized human proximal tubule (HK-2) cells were treated with H(2)O(2). H(2)O(2) caused dose- and time-dependent HK-2 cell death that was measured by lactate dehydrogenase release and trypan blue dye uptake. Adenosine protected against H(2)O(2)-induced HK-2 cell death by means of A(1)- and A(2a)-AR activation. A(1)-AR-mediated protection involves pertussis toxin-sensitive G proteins and protein kinase C, whereas A(2a)-AR-mediated protection involves protein kinase A activation by means of cAMP and activation of the cAMP response element binding protein. Moreover, protein kinase A activators (forskolin and Sp-isomer cAMP) also protected HK-2 cells against H(2)O(2) injury. De novo gene transcription and protein synthesis are required for both A(1)- and A(2a)-AR-mediated cytoprotection as actinomycin D and cycloheximide, respectively, blocked cytoprotection. Chronic treatments with a nonselective AR agonist abolished the protection by adenosine. Moreover, chronic treatments with a nonselective AR antagonist increased the endogenous tolerance of HK-2 cells against H(2)O(2). We concluded that A(1)- and A(2a)-AR activation protects HK-2 cells against H(2)O(2)-induced injury by means of distinct signaling pathways that require new gene transcription and new protein synthesis.
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PMID:Adenosine attenuates oxidant injury in human proximal tubular cells via A(1) and A(2a) adenosine receptors. 1193 94

In order to understand the intracellular mechanism of hypoxic preconditioning,we investigated the effects of G(i/o) protein, phospholipase C and adenylyl cyclase/cyclic adenosine monophosphate (cAMP) on the survival rate and lactate dehydrogenase (LDH) release of cultured neonatal rat cardiomyocytes during the reoxygenation following 3 h of hypoxia. Cardioprotection was conferred by a brief episode of hypoxia followed by reoxygenation. The obtained results are as follows: (1) Hypoxic preconditioning (25 min of hypoxia and 30 min of reoxygenation) increased the survival rate and decreased the release of LDH in the myocytes suffering from sustained hypoxia-reoxygenation. (2) Reducing the intracellular cAMP by N-ethylmaleimide, an inhibitor of adenylyl cyclase, could mimic the cardioprotection of the preconditioning. (3) Inhibition of G(i/o) protein by pertussis toxin abolished the cardioprotection of hypoxic preconditioning, with reduction of the survival rate and increase of the release of LDH. (4) U-73122 could not abolish the protective effect of hypoxic preconditioning. (5) When intracellular cAMP was increased by using 8-Br-cAMP, a high membrane permeable cAMP analogue, or forskolin, a specific adenylyl cyclase activator, the survival rate was lower and LDH activity higher than those in preconditioning myocytes. The results indicate that G(i/o) protein is a crucial component, in cardioprotection of hypoxic preconditioning in neonatal rat cardiomyocytes. Activation of phospholipase C does not seem to be involved in the intracellular signal pathway underlying the cardioprotective effect of the preconditioning.
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PMID:[Evaluation of G(i/o) protein signal transduction pathway in cardioprotection of hypoxic preconditioning]. 1196 75


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