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 MDA-468 human breast cancer cell line has an amplified epidermal growth factor (EGF) receptor gene (20 x) and correspondingly overexpresses the EGF receptor. Since this cell line is growth inhibited by supra-physiological levels of EGF in tissue culture, it has been possible to select variant cells which have lost the chromosome bearing the amplified EGF receptor domain and which are capable of growing in high levels of EGF. One such cell line (MDA-468-S4) shows an absolute requirement for EGF for growth in anchorage-independent tissue culture conditions. We have utilized MDA-468 and MDA-468-S4 to examine the intracellular transduction of EGF signals leading to growth inhibition and proliferation, respectively. We report that in anchorage-independent conditions, pertussis toxin can abrogate both the EGF-dependent growth inhibition in MDA-468 cells and the EGF-dependent cell proliferation in MDA-468-S4 cells. This inhibition is paralleled by the ADP-ribosylation of an endogenous 41,000-dalton membrane protein in both MDA-468 and MDA-468-S4 cells. In contrast, the toxin does not prevent the transient, augmented expression of c-myc and c-fos mRNA seen in response to EGF in both cell types. These data suggest 1) the notion of more than one simultaneous, parallel, intracellular EGF-dependent signal transduction pathway and 2) G-protein involvement in at least one pathway mandatory for the growth modulating responses to EGF in anchorage-independent conditions, but distinct from that inducing c-myc and c-fos mRNA expression.
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PMID:G-protein-mediated epidermal growth factor signal transduction in a human breast cancer cell line. Evidence for two intracellular pathways distinguishable by pertussis toxin. 312 85

Chinese hamster ovary (CHO) cells cluster in the presence of pertussis toxin, a response that is correlated with the ADP-ribosylation of a Mr = 41,000 membrane protein by the toxin. A ricin-resistant line of CHO cells (CHO-15B) which specifically lacks the terminal NeuAc----Gal beta 4GlcNAc oligosaccharide sequence on glycoproteins did not cluster in response to pertussis toxin. These cells do contain the Mr = 41,000 protein substrate for the enzymatic activity of the toxin which suggests that pertussis toxin, like certain plant lectins, does not bind to or is not internalized by the CHO-15B cells. There was no evidence of pertussis toxin binding to gangliosides or neutral glycolipids isolated from CHO cells but the toxin bound to a Mr = 165,000 component in N-octyglucoside extracts of CHO cells that had been separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotted to nitrocellulose. Plant lectins from Ricinus communis and Erythina cristagalli detected a similar size band in CHO cells and also did not react with CHO-15B cells. Unlike pertussis toxin, these plant lectins recognized two other major bands in CHO cell extracts and reacted best after sialidase treatment of nitrocellulose transfers containing CHO cell extracts. Conversely, sialidase treatment abolished binding a pertussis toxin and wheat germ agglutinin, a plant lectin that reacts with multivalent sialic acid residues on glycoproteins, to the Mr = 165,000 band. Purified B oligomer of pertussis toxin also uniquely detected a Mr = 165,000 component in CHO cell extracts while the A subunit of pertussis toxin was unreactive. These results indicate that pertussis toxin binds to a CHO cell glycoprotein with N-linked oligosaccharides and that sialic acid contributes to the complementary receptor site for the toxin. In addition, they suggest that a glycoprotein may serve as a cell surface receptor for pertussis toxin and that this interaction is mediated by a lectin-like binding site located on the B oligomer.
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PMID:Lectin-like binding of pertussis toxin to a 165-kilodalton Chinese hamster ovary cell glycoprotein. 335 Aug 15

Antisera raised against the carboxy-terminal decapeptide (KENLKDCGLF) of transducin-alpha detected the 40 kDa, major pertussis toxin substrate of human neutrophils. The antisera also detected this protein in undifferentiated HL-60 and U937 cells, and revealed an approx. 2-fold increase in protein/mg membrane protein with differentiation into mature phagocytic cells. The results provide direct immunochemical evidence for the presence of a novel, pertussis toxin-sensitive guanine nucleotide-binding protein in human leukocytes.
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PMID:Detection of the major pertussis toxin substrate of human leukocytes with antisera raised against synthetic peptides. 346 5

Pretreatment of cultured bovine adrenal chromaffin cells with pertussis toxin facilitated nicotine-induced catecholamine release. This facilitation was correlated with the ability of the toxin to catalyze the ADP-ribosylation of an approximately 40-kDa membrane protein. The actions of the toxin were reversed by isonicotinamide, an inhibitor of ADP-ribosylation. Catecholamine release due to high K+ and muscarine was also enhanced by pertussis toxin. In all cases, 45Ca2+ uptake was unaltered in cells treated with the toxin. These results suggest that ADP-ribosylation of a 40-kDa membrane protein facilitates catecholamine release from bovine chromaffin cells without affecting 45Ca2+ uptake.
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PMID:Pertussis toxin facilitates secretagogue-induced catecholamine release from cultured bovine adrenal chromaffin cells. 357 47

Pertussis toxin catalyzes incorporation of 20.2 pmol of ADP-ribose/mg of protein into approximately 40-kDa protein(s) in human neutrophil membranes compared with 14.1 pmol/mg in bovine brain membranes. Based on these measurements we estimate that pertussis toxin substrate(s) should represent at least 0.085% of total membrane protein in neutrophils. Both brain and neutrophil membranes show high concentrations (0.34 versus 0.16% of total membrane protein, respectively) of the common beta subunit of guanine nucleotide binding proteins. Affinity purified antibodies specific for Go-alpha fail to detect any protein in immunoblots of neutrophil membranes (150 micrograms) under conditions where as little as 10 ng of purified Go-alpha is detectable, and Go-alpha is readily detected in brain membranes (100 micrograms). An antiserum against transducin that cross-reacts strongly with Gi-alpha, detects as little as 5 ng of purified Gi-alpha and readily detects Gi-alpha in brain membranes, but in neutrophil membranes, the antiserum detects an approximately 40-kDa band that corresponds to less than 10% of the expected amount of pertussis toxin substrate(s). The results show that human neutrophil membranes contain relatively large amounts of pertussis toxin substrate(s), but that the predominant pertussis toxin substrate is immunochemically distinct from previously identified substrates, transducin, Gi, and Go.
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PMID:Immunochemical evidence for a novel pertussis toxin substrate in human neutrophils. 371 Nov 24

When WBC264-9C cells are preincubated with pertussis toxin, chemotaxis is inhibited and ADP-ribosylation of a membrane protein with a subunit Mr 41,000 is observed. Both the inhibition of chemotaxis and the ADP-ribosylation by pertussis toxin display a similar time lag, temperature dependence, and pertussis toxin-concentration dependence. Although the inhibition of chemotaxis and the ADP-ribosylation of the membrane protein are qualitatively correlated, nearly complete inhibition of chemotaxis occurs when there is only partial ADP-ribosylation of the membrane protein. Pertussis toxin-catalyzed ADP-ribosylation of the Mr 41,000 protein in WBC264-9C membranes is stimulated by GDP, GTP, and to a lesser extent by GMP; the nonhydrolyzable GTP analog guanosine 5'-[beta, gamma-imido]triphosphate has no effect. WBC264-9C membranes have a high-affinity GTPase activity, which is partially inhibited in membranes from pertussis toxin-treated cells. Neither GTPase activity nor adenylate cyclase activity in membranes from WBC264-9C cells is affected by fMet-Leu-Phe, an attractant for these cells. Our results suggest that a guanine nucleotide binding protein may be involved in chemotaxis, but they do not indicate an involvement of adenylate cyclase.
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PMID:Pertussis toxin inhibition of chemotaxis and the ADP-ribosylation of a membrane protein in a human-mouse hybrid cell line. 385 5

A 68-kilodalton (kd) outer membrane protein antigen of Bordetella bronchiseptica has been identified by using monoclonal antibodies that recognized two nonoverlapping determinants. Antibody BB05 also reacted with homologous proteins from Bordetella pertussis and Bordetella parapertussis but not with another 12 organisms from various bacterial genera. Passive injection of BB05 antibody protected mice from aerosol infection with B. bronchiseptica as shown by reduced mortality and reduced pathology of turbinate bones. The 68-kd B. bronchiseptica antigen was purified by BB05-based affinity chromatography and evaluated for its potency to immunize mice actively against either intraperitoneal or aerosol challenge with B. bronchiseptica. Immunization with the 68-kd antigen in incomplete Freund adjuvant significantly reduced the levels of mortality in intraperitoneally challenged mice. In the aerosol infection model, injection of the 68-kd antigen with complete or incomplete Freund adjuvant or saponin reduced the bacterial counts in the lungs of infected mice. These results suggest that the 68-kd protein may represent a potential "protective" antigen of B. bronchiseptica.
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PMID:Identification of a 68-kilodalton protective protein antigen from Bordetella bronchiseptica. 397 52

The intermediary role of the putative inhibitory regulatory membrane protein "Ni" in the "antigonadal" activity of the neurohypophysial hormones was investigated in vitro with the use of a primary culture of rat testicular cells. To this end, use was made of the pertussis toxin (PT) probe, an exotoxin of Bordetella pertussis presumed to modify and inactivate a membrane protein related to or identical with Ni. Testicular cells were pretreated with PT (70 ng/ml) for 24 h, a duration of exposure known to result in a maximal PT effect. Thereafter, the cells were cultured for an additional 48 h in the absence or presence of hCG (10 ng/ml), with or without a maximal inhibitory dose (10(-6) M) of the neurohypophysial principle arginine vasotocin (AVT). Although concomitant treatment of control cells with AVT produced a profound (95%) inhibition of hCG-stimulated testosterone accumulation, PT pretreatment resulted in a long-lasting (greater than 4 days) abolition of this "antigonadal" effect. Furthermore, pretreatment with PT resulted in significant (P less than 0.05) augmentation of the hCG-stimulated accumulation of extracellular cAMP (1.5- to 2.0-fold) and testosterone (1.7- to 3.8-fold), presumably as a result of abolition of the "basal" tonic inhibition of adenylate cyclase activity. Taken together, these findings constitute the first demonstration of the involvement of Ni in the "antigonadal" activity of the neurohypophysial hormones and in the regulation of testicular function, thereby raising the intriguing possibility that testicular Ni may serve as the coupling unit of inhibitory receptors other than those for the neurohypophysial hormones, integrating varied incoming signals of endocrine, paracrine or autocrine nature.
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PMID:"Antigonadal" activity of the neurohypophysial hormones in cultured rat testicular cells: abolition by pertussis toxin. 608 80

Treatment of guinea pig neutrophils with pertussis toxin (islet-activating protein; IAP) results in inhibition of N-formyl peptide receptor-mediated release of arachidonic acid and granular enzymes. Inhibition by the toxin is specific, in that responses to the calcium ionophore A23187 are not affected. The action of the toxin is not associated with alterations in cellular concentrations of cyclic AMP but is correlated with the ability of the toxin to catalyze the ADP-ribosylation of a 41,000 dalton membrane protein. This protein comigrates on SDS-polyacrylamide gels with the alpha subunit of Gi, the inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. It is likely that this G protein is involved in receptor-mediated signal transduction in neutrophils by mechanisms that do not involve cyclic AMP.
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PMID:Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin. 609 10

Two Bordetella pertussis antigen preparations, outer membrane protein (OMP) and filamentous haemagglutinin (FHA), and a standard vaccine were used to immunize rabbits, and the effects on nasopharyngeal colonization by the organism were determined. Antibodies were measured in serum and in nasal washes by ELISA before and after challenge of the rabbits with 10(6) bacteria of strain M2. Recoveries of B. pertussis in nasal washes were used to assess colonization, which in controls persisted for at least 65 days. Some rabbits of all the immunized groups showed enhanced clearance, but there was no correlation between the elimination of B. pertussis and serum antibodies to OMP, FHA, lipopolysaccharide, lymphocytosis-promoting factor or agglutinogen 3. In contrast, nasal IgA antibody to FHA showed significant inverse correlation with bacterial persistence. Such antibody was induced by the OMP preparation as well as by FHA, but to different extents depending on the immunization schedule and adjuvant used.
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PMID:Rabbit nasopharyngeal colonization by Bordetella pertussis: the effects of immunization on clearance and on serum and nasal antibody levels. 628 59


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