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)

Interleukin-3 stimulates the survival and proliferation of the FDCP-Mix 1 multipotent stem cell line. We have investigated the possible involvement of a guanyl nucleotide regulatory (G) protein(s) in the IL-3 stimulated proliferative response. We report here that pertussis toxin (PT) can partially inhibit IL-3 stimulated DNA synthesis and that this inhibition is bypassed by TPA. The ADP-ribosylation of the PT substrate G protein in vivo is complete in 2 hours without concomitant inhibition of IL-3 stimulated hexose transport or Na+/H+ exchange. When loaded into FDCP-Mix 1 cells fluoroaluminate and GTP-gamma-S, which can directly activate G proteins, are not capable of mimicking the effects of IL-3. Evidence is also presented that IL-3 does not stimulate a membrane-bound high affinity GTPase activity in the FDCP-Mix 1 cell line. These data suggest that a PT substrate G protein(s) can influence the IL-3 signalling cascade in an indirect or permissive manner, but that the IL-3 receptor does not directly couple to a PT substrate G protein.
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PMID:IL-3 stimulated haemopoietic stem cell proliferation: evidence for G protein independent mitogenic signalling events. 132 14

Epidermal growth factor (EGF), a mitogen for renal proximal tubule cells, activated the hexose monophosphate (HMP) shunt in renal proximal tubule cells (Stanton, R. C., and Seifter, J. L. (1988) Am. J. Physiol. 254, C267-C271). We therefore evaluated the effect of EGF on the HMP shunt enzymes glucose 6-phosphate dehydrogenase (G6PD, the rate-limiting enzyme) and 6-phosphogluconate dehydrogenase. Rat renal cortical cells (RCC) were incubated with either EGF or platelet-derived growth factor (PDGF) and then assayed for G6PD and 6-phosphogluconate dehydrogenase activities. EGF and PDGF increased G6PD activity by 25 and 27% respectively. Although phorbol myristate acetate (PMA), ionomycin, PMA + ionomycin, and 8-bromo-cyclic AMP had no significant effect on the activity, a 5-min preincubation with PMA potentiated the activation of G6PD by PDGF. Growth factor activation of G6PD was also seen in a fibroblast and epithelial cell line. None of the agents affected 6-phosphogluconate dehydrogenase activity in the RCC or in the cell lines. Further exploration into a possible mechanism for G6PD activation revealed that growth factors caused release of G6PD from a structural element within the cell. Streptolysin O permeabilization of RCC did not cause significant release of G6PD. However, within 1 min of addition of EGF or PDGF to permeabilized cells, G6PD was released into the cell supernatant. The nonhydrolyzable analog of GTP, guanosine 5'-O-(thiotriphosphate), caused a similar release of G6PD. Preincubation with pertussis toxin or guanyl-5'-yl thiophosphate inhibited the PDGF but not the EGF effect. Although the data do not establish a definitive proof linking G6PD release and G6PD activation, these results suggest that they are related. Thus, growth factor stimulation of the HMP shunt likely occurs by a novel mechanism associated with release of bound G6PD.
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PMID:Rapid release of bound glucose-6-phosphate dehydrogenase by growth factors. Correlation with increased enzymatic activity. 206 19

Despite numerous reports, the role of tumor necrosis factor (TNF) in polymorphonuclear leukocyte (PMN) function remains controversial. We found TNF to be a potent, pertussis toxin-independent stimulator of PMN adhesion (ED50 2.6 pM). TNF-stimulated PMN under adherent conditions released up to 65% of their transcobalamine content (ED50 3.9 pM) and increased their burst activity 10-fold (ED50 3.2 pM) as measured by the hexose monophosphate shunt, whereas PMN held in suspension hardly degranulated at all and only little burst activity was demonstrable. However, preincubation of PMN with TNF in suspension led to a decrease in cellular adhesiveness, degranulation, and burst activity in response to a secondary stimulus of TNF under adherent conditions, although cells remained fully responsive toward phorbol myristate acetate. A concomitant dose-dependent decline of TNF receptor numbers that correlated well with the inhibition of PMN function (r = 0.91) suggests receptor down-regulation as the mechanism of functional PMN deactivation. Remarkably, preincubation with other PMN stimuli such as N-formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, leukotriene B4, complement component fragment 5a (C5a)/C5a (desarginated), and endotoxin also led to a reduction of TNF-specific PMN responses (cross-deactivation) from 35% (LTB4) to 90% (endotoxin), corresponding with the down-regulation of TNF receptors. Deactivation and receptor down-regulation are independent of pertussis toxin-sensitive G proteins and protein kinase C but seemed to depend on changes in calcium metabolism. Granulocyte hyporesponsiveness towards TNF in sepsis (with elevated blood levels of endotoxin and TNF) might be a mechanism of self-protection or, to the contrary, might impair a possibly central mode of host defense.
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PMID:The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factor-induced neutrophil responses by receptor down-regulation. 216 42

Interleukin 3 (IL-3) stimulates several biochemical and biological responses in IL-3-dependent tissue culture cells. We examined the possibility that guanyl nucleotide regulatory (G) proteins may transduce signals from IL-3 receptors. We report here that pertussis toxin (PT), which can covalently modify a subclass of G proteins, is capable of inhibiting IL-3-stimulated proliferation in a dose-dependent fashion. PT inhibition of IL-3-stimulated proliferation could be overcome by using the Ca++ ionophore A23187 in conjunction with TPA. PT could also inhibit IL-3-stimulated hexose transport. In the absence of IL-3, hexose transport could be stimulated by introducing GTP-gamma S into intact cells. From these data we propose that IL-3 receptors transduce signals via a PT-sensitive G protein(s).
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PMID:Interleukin 3-stimulated proliferation is sensitive to pertussis toxin: evidence for a guanyl nucleotide regulatory protein-mediated signal transduction mechanism. 253 25

When stimulated, neutrophils undergo a complex change in cytoplasmic pH (pHi): an incipient acidification, followed by an alkalinization which is due to activation of Na+/H+ exchange. When the latter is inhibited by amiloride or by removal of extracellular Na+, the actual magnitude of the initial acidification can be fully appreciated. The acidification is thought to be of metabolic origin, but the precise origin of the H+ (equivalents) remains undefined. We used adenosine, a modulator of neutrophil responsiveness, to identify the source of metabolic acid in cells stimulated by either formylmethionylleucylphenylalanine (fMet-Leu-Phe) or 12-O-tetradecanoylphorbol 13-acetate (TPA). Pretreatment of the cells with adenosine inhibited the fMet-Leu-Phe-induced respiratory burst, but secretion of specific and azurophilic granules, as well as aggregation were unaffected. In fMet-Leu-Phe-treated cells, adenosine reduced the acidification recorded in Na+-free media, but had no effect on the activation of the Na+/H+ antiport. Adenosine had little or no effect on the TPA-induced responses, including the pHi changes. The respiratory burst, as well as the cytoplasmic acidification were also inhibited in parallel by pretreating the cells with 'islet-activating protein' from Bordetella pertussis. It was concluded that activation of the NADPH-oxidase and/or the associated stimulation of the hexose monophosphate shunt play a major role in the metabolic acidification of stimulated neutrophils.
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PMID:Cytoplasmic pH regulation in activated human neutrophils: effects of adenosine and pertussis toxin on Na+/H+ exchange and metabolic acidification. 302 27

Addition of fibroblast growth factor to quiescent cultures of Swiss 3T3 cells stimulated the membrane transport of 2-deoxyglucose. Treatment of the cells with pertussis toxin (islet-activating protein) inhibited fibroblast growth factor-stimulated hexose transport. 5'-Guanylyl imidodiphosphate (p[NH]ppG), a non hydrolyzable analogue of GTP, increased the number of hexose carriers in the plasma membrane of saponin-permeabilized cells. These results suggest that guanine nucleotide binding protein may be involved in the regulation of hexose transport system by fibroblast growth factor in Swiss 3T3 cells.
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PMID:Inhibition by pertussis toxin of fibroblast growth factor-stimulated hexose transport in Swiss 3T3 cells. 311 8

The effects of pertussis toxin (PT) treatment on insulin-stimulated myristoyl-diacylglycerol (DAG) generation, hexose transport, and thymidine incorporation were studied in differentiated BC3H-1 myocytes. Insulin treatment caused a biphasic increase in myristoyl-DAG production which was abolished in myocytes treated with PT. There was no effect of PT treatment on basal (nonstimulated) myristoyl-DAG production. Insulin-stimulated hydrolysis of a membrane phosphatidylinositol glycan was blocked by PT treatment. ADP-ribosylation of BC3H-1 plasma membranes with [32P]NAD revealed a 40-kDa protein as the major PT substrate in vivo and in vitro. The time course and dose dependence of the effects of PT on diacylglycerol generation correlated with the in vivo ADP-ribosylation of the 40-kDa substrate. Pertussis toxin treatment resulted in a 71% attenuation of insulin-stimulated hexose uptake without effect on either basal or phorbol ester-stimulated uptake. The stimulatory effects of insulin and fetal calf serum on [3H]thymidine incorporation into quiescent myocytes were attenuated by 61 and 59%, respectively, when PT was added coincidently with the growth factors. Nonstimulated and EGF-stimulated [3H]thymidine incorporation was unaffected by PT treatment. These data suggest that a PT-sensitive G protein is involved in the cellular signaling mechanisms of insulin.
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PMID:Pertussis toxin treatment attenuates some effects of insulin in BC3H-1 murine myocytes. 328 21

Recent advances in insulin secretion indicate that pertussis toxin abolishes the inhibition by alpha 2 adrenoceptor activation of insulin release by the pancreas. Pertussis toxin adenosine diphosphate (ADP) ribosylates an inhibitory guanine nucleotide-binding protein (Ni) involved in inhibition of adenylate cyclase. The decrease in cyclic adenosine monophosphate (AMP) by epinephrine may account for its inhibition of insulin release. Insulin interaction with its receptor results in an increase in the tyrosine protein kinase activity of the receptor. Second messengers for insulin are generated, hexose transport is accelerated, and a cyclic AMP-independent protein kinase is activated that phosphorylates at serinethreonine residues. The activity of membrane-bound enzymes such as adenylate cyclase and Ca2+-Mg2+-ATPase is affected. The relative importance of these effects of insulin in its regulation of cellular metabolism remains to be established.
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PMID:Insulin secretion and action. 614 90

To investigate the possibility that insulin-stimulated glucose uptake in C6 cells is due to transactivation of a G protein-mediated pathway, the role of Gq alpha in insulin signaling was studied. Insulin stimulation of [3H]2-deoxy-D-glucose (2DG) uptake by C6 cells was time- and concentration-dependent: at a concentration of 1 microM, insulin stimulated 2DG uptake by C6 cells by about 30% (p < 0.05). Pertussis toxin treatment of C6 cells did not alter the ability of insulin (1 microM) to promote 2DG uptake, ruling out the involvement of Gion in insulin-stimulated hexose uptake. Next, C6 cells were transfected with Gq alpha cDNA for 48 h, challenged with 1 microM insulin, and 2DG uptake by the cells was determined. Insulin-stimulated 2DG uptake was 1.14 +/- 0.03 and 1.75 +/- 0.19 nmol/min/mg protein in mock- and Gq alpha-transfected cells, respectively (p < 0.05); insulin stimulated 2DG uptake in Gq alpha-transfected cells by 54%. These results suggest an involvement of Gq alpha in the transactivation of the G protein signal transduction pathway by insulin.
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PMID:Role of Gq alpha in insulin-stimulated glucose uptake by C6 glioma cells. 924 40

The role of G proteins in glucose uptake was investigated using C6 glioma cells. Carbachol (an agonist acting via G protein coupled receptors) and 5'-guanylylimidodiphosphate (Gpp(NH)p; a nonhydrolysable guanine nucleotide analog which bypasses the receptors and directly activates G proteins) stimulated [3H]2-deoxy-D-glucose (2DG) uptake by C6 cells, suggesting that hexose uptake is a G protein-mediated process. To identify the G protein involved in glucose uptake by C6 cells, the effect of carbachol on 2DG uptake was examined in the presence of pertussis toxin. Pertussis toxin treatment did not alter the ability of C6 cells to respond to carbachol, ruling out the involvement of G(i alpha) in 2DG uptake. C6 cells were transfected with G(q alpha) or GLUT1 cDNA for 48 h, exposed to 1 mM carbachol for 2 h, and processed for 2DG uptake. Carbachol stimulated 2DG uptake in both G(q alpha) and GLUT1-transfected cells. Gpp(NH)p, also stimulated 2DG uptake in G(q alpha) and GLUT1-transfected cells. These results suggest that muscarinic receptor coupling to G(q alpha) regulates hexose uptake in C6 cells.
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PMID:Glucose uptake by C6 glioma cells is mediated by G(q alpha). 959 59


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