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)

A monoclonal antibody against GM3 ganglioside (GM3Ab) was found to trigger differentiation of Neuro-2a cells in culture. The differentiation of Neuro-2a cells by GM3Ab was accompanied by increased levels of intracellular serotonin and amino acid neurotransmitters viz. aspartate, glutamate, glutamine, glycine and taurine. Further study indicated that the increase in the serotonin level was not due to a higher rate of serotonin synthesis but rather to a higher rate of active transport of serotonin from the medium. Studies on the cell surface gangliosides revealed that unlike the proliferating cells, the GM3Ab-mediated differentiated cells contained higher gangliosides in addition to GM3 and GM2 gangliosides. Analysis of total cellular proteins indicated the appearance of a 25 kDa protein, pI 5.4, in the GM3Ab-treated cells--a small amount of this protein was observed in dibutyryl cAMP (Bt2cAMP)-treated cells, however, the protein was totally absent in the 5-bromo-2'-deoxyuridine (BrdU)-treated cells. Investigation of the mode of action of GM3Ab indicated that the cellular differentiation was due to increased cAMP accumulation resulting from an increase in the adenylate cyclase activity. Further studies with different agents affecting protein kinase C (PKC) activity and direct assay of PKC ruled out the possibility that GM3Ab mediated its effect via PKC. This GM3Ab-induced differentiation could be inhibited by protein kinase A (PKA) inhibitor, H8, but could not be inhibited by sphingosine, an inhibitor of PKC. Pertussis toxin could mimic the effect of GM3Ab, suggesting that GM3Ab caused the elevation in the adenylate cyclase activity by reducing the Gi-protein inhibition of the adenylate cyclase. The data suggests that GM3Ab, after interaction with cell surface GM3, elevated intracellular cAMP level by withdrawing the inhibitory effect of some undefined factor(s) present in culture medium which normally keeps adenylate cyclase activity low through activation of Gi-protein.
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PMID:Differentiation of Neuro-2a neuroblastoma cells by an antibody to GM3 ganglioside. 132 94

The adherence of the human respiratory pathogen, Bordetella pertussis, to purified glycosphingolipids was investigated using thin layer chromatography overlay assays. Both virulent and avirulent strains of B. pertussis bound to asialo GM1. The bacterium did not bind to the gangliosides GM1, GD1a, GD1b, and GT1b, nor to lactosylceramide, trihexosylceramide, globoside, or Forssman antigen. However, after treatment of the chromatography plates with sialidase, B. pertussis bound to the gangliosides GM1, GM2, GD1a, GD1b, and GT1b but not to GM3. Comparison of the oligosaccharide structures of these gangliosides suggests that the minimum sugar structure needed for avid bacterial binding is GalNAc beta 4Gal. This structure has been previously implicated as a receptor for other human respiratory pathogens (Krivan, H. C., Roberts, D. D., Ginsburg, V. (1988) Proc. Natl. Acad. Sci. U.S.A 85, 6157-6161). Virulent strains of B. pertussis also bound specifically to sulfatide. This response was dose-dependent and inhibited by the anionic polysaccharide dextran sulfate. The sulfated-sugars dextran sulfate, fucoidan, and heparin inhibited the attachment of virulent strains of B. pertussis to human WiDr cells and to hamster trachea cells indicating that sulfatides on the surface of mammalian cells may function as a receptor for B. pertussis. The occurrence of both sulfatides and asialo GM1 in human lung and trachea suggests that these glycolipids may serve as specific receptors for B. pertussis.
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PMID:Adhesion of Bordetella pertussis to sulfatides and to the GalNAc beta 4Gal sequence found in glycosphingolipids. 191 2

We have recently reported that gangliosides act as inhibitors of ADP-ribosyltransferases and NAD+ glycohydrolases (NADase) of pertussis toxin and the C3 exoenzyme from Clostridium botulinum (Hara-Yokoyama, M., Hirabayashi, Y., Irie, F., Syuto, B., Moriishi, K., Sugiya, H., and Furuyama, S. (1995) J. Biol. Chem. 270, 8115-8121). Here, we investigated the effect of gangliosides on the enzymatic activity of leukocyte cell surface antigen CD38, which is identified as an ecto-NADase (Kontani, K., Nishina, H., Ohoka, Y., Takahashi, K., and Katada, T. (1993) J. Biol. Chem. 268, 16895-16898). Gangliosides GM1a and GQ1balpha inhibited the NADase activity in the immunoprecipitate of anti-CD38 antibody from the membrane extract of retinoic acid-treated human leukemic HL-60 cells. Gangliosides also inhibited the NADase activity of the extracellular domain of CD38 antigen that was deprived of the transmembrane domain and was expressed in Escherichia coli as a fusion protein with maltose-binding protein (MBP-CD38). The order of the inhibitory effect of purified ganglioside species on the NADase activity on MBP-CD38 was as follows: GQ1balpha > GT1b, GQ1b > GD1a, GD1b, GM1a, GM1b, GD3, GM3. GQ1balpha inhibited the NADase of MBP-CD38 in a noncompetitive manner versus NAD+ with a Ki value of about 0.3 microM. Neither ceramide nor the oligosaccharide moiety of GQ1balpha had an effect on the NADase activity. GQ1balpha, GT1b, and GQ1b also efficiently inhibited the ADP-ribosyl cyclase activity of MBP-CD38. At present, gangliosides are the only endogenous species that can block the enzymatic activity of CD38 antigen. The present results suggest a potential role of gangliosides as inhibitors of the ecto-NADases.
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PMID:Inhibition of NAD+ glycohydrolase and ADP-ribosyl cyclase activities of leukocyte cell surface antigen CD38 by gangliosides. 866 99

Previous studies have shown GM1 ganglioside to play a crucial role in regulating excitatory opioid receptor function, which may underlie some aspects of opioid dependence, tolerance, and supersensitivity. To study the mechanism of this receptor modulation we have employed CHO cells containing a single, transfected opioid receptor of the delta-type. When forskolin was employed to elevate cAMP the reduction affected by 10 microM DADLE was counteracted by preincubation of the cells with GM1. No effect was observed with GD1a, GD1b, GT1b GM3, or the GM1 derivative, GM1-OH. In pertussis toxin-treated cells 10 nM DADLE increased basal levels of cAMP after preincubation with as little as 10 nM GM1. The results suggest conformational alteration of the opioid receptor from a form coupled primarily to G(i)/G(o) to one also capable of interacting with G(s).
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PMID:Interaction of the delta-opioid receptor with GM1 ganglioside: conversion from inhibitory to excitatory mode. 907 76

The binding of cholera toxin, tetanus toxin and pertussis toxin to ganglioside containing solid supported membranes has been investigated by quartz crystal microbalance measurements. The bilayers were prepared by fusion of phospholipid-vesicles on a hydrophobic monolayer of octanethiol chemisorbed on one gold electrode placed on the 5 MHz AT-cut quartz crystal. The ability of the gangliosides GM1, GM3, GD1a, GD1b, GT1b and asialo-GM1 to act as suitable receptors for the different toxins was tested by measuring the changes of quartz resonance frequencies. To obtain the binding constants of each ligand-receptor-couple Langmuir-isotherms were successfully fitted to the experimental adsorption isotherms. Cholera toxin shows a high affinity for GM1 (Ka = 1.8.10(8)M-1), a lower one for asialo-GM1 (Ka = 1.0.10(7)M-1) and no affinity for GM3. The C-fragment of tetanus toxin binds to ganglioside GD1a, GD1b and GT1b containing membranes with similar affinity (Ka approximately 10(6)M-1), while no binding was observed with GM3. Pertussis toxin binds to membranes containing the ganglioside GD1a with a binding constant of Ka = 1.6.10(6)M-1, but only if large amounts (40 mol%) of GD1a are present. The maximum frequency shift caused by the protein adsorption depends strongly on the molecular structure of the receptor. This is clearly demonstrated by an observed maximum frequency decrease of 99 Hz for the adsorption of the C-fragment of tetanus toxin to GD1b. In contrast to this large frequency decrease, which was unexpectedly high with respect to Sauerbrey's equation, implying pure mass loading, a maximum shift of only 28 Hz was detected after adsorption of the C-fragment of tetanus toxin to GD1a.
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PMID:Quartz crystal microbalance investigation of the interaction of bacterial toxins with ganglioside containing solid supported membranes. 927 95

Prosaposin, the precursor of saposins A, B, C, and D, was recently identified as a neurotrophic factor in vitro as well as in vivo. Its neurotrophic activity has been localized to a linear 12-amino acid sequence located in the NH2-terminal portion of the saposin C domain. In this study, we show the colocalization of prosaposin and ganglioside GM3 on NS20Y cell plasma membrane by scanning confocal microscopy. Also, TLC and western blot analyses showed that GM3 was specifically associated with prosaposin in immunoprecipitates; this binding was Ca2+-independent and not disassociated during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The association of prosaposin-GM3 complexes on the cell surface appeared to be functionally important, as determined by differentiation assays. Neurite sprouting, induced by GM3, was inhibited by antibodies raised against a 22-mer peptide, prosaptide 769, containing the neurotrophic sequence of prosaposin. In addition, pertussis toxin inhibited prosaptide-induced neurite outgrowth, as well as prosaptide-enhanced ganglioside concentrations in NS20Y cells, suggesting that prosaposin acted via a G protein-mediated pathway, affecting both ganglioside content and neuronal differentiation. Our findings revealed a direct and tight GM3-prosaposin association on NS20Y plasma membranes. We suggest that ganglioside-protein complexes are structural components of the prosaposin receptor involved in cell differentiation.
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PMID:Colocalization and complex formation between prosaposin and monosialoganglioside GM3 in neural cells. 983 29

Gangliosides, sialic acid-containing glycophospholipids, accumulate in atherosclerotic vessels and appear to regulate the proliferation of various cell types. Furthermore, vascular smooth muscle cell (VSMC) proliferation is associated with the development and progression of cardiovascular diseases. To demonstrate whether gangliosides are able to modulate the VSMC growth, the effect of gangliosides GM1, GM2, and GM3 on cell DNA synthesis and cell number has been examined. Moreover, we investigated possible intracellular mechanisms by which GM1 and GM2 elicit their mitogenic effects. Stimulation of VSMCs with GM1 and GM2 resulted in a dose-dependent increase in DNA synthesis and cell number, whereas GM3 caused a decrease in DNA synthesis. GM1 and GM2 (50 micromol/L) stimulate phosphorylation of extracellular signal-regulated kinases (ERKs) 1 and 2 and phosphorylation of the c-Jun N-terminal kinase (JNK), with a maximum at 15 minutes, but they do not have an effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). GM3 (50 micromol/L), on the other hand, does not stimulate any of the 3 aforementioned MAPKs. Pretreatment of the cells with 20 micromol/L PD 098,059 caused a complete inhibition of ERK1/2 and JNK MAPK, whereas pretreatment with a Ras (farnesyl transferase) inhibitor did not abrogate the GM1- and GM2-induced ERK1/2 phosphorylation. Furthermore, GM1 and GM2 did not activate Raf-1 kinase. Interestingly, pretreatment of VSMCs with 100 nmol/L pertussis toxin resulted in a complete inhibition of the ERK1/2 phosphorylation. Finally, the GM1- and GM2-induced increase in cell number was significantly inhibited by PD 098,059. We may conclude that GM1 and GM2 stimulate ERK1/2 via a pertussis toxin-sensitive G(i)-coupled receptor through a Raf-1 kinase-independent pathway. Moreover, the GM1- and GM2-induced VSMC growth is ERK1/2 dependent.
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PMID:Gangliosides GM1 and GM2 induce vascular smooth muscle cell proliferation via extracellular signal-regulated kinase 1/2 pathway. 1171 93

Tetanus neurotoxin (TeNT), pertussis toxin (PT) and pertussis filamentous haemagglutinin (FHA) are major virulence factors of Clostridium tetani and Bordetella pertussis, which are the causative agents of tetanus and whooping cough respectively. Inactivated forms of these virulence factors are the protein components of vaccines against these diseases. Here we report microcalorimetric studies to characterize these proteins. The microcalorimetric titration curves of TeNT with micelles of gangliosides GD1b, GT1b and GQ1b were biphasic. For these gangliosides a high-affinity binding site (KD 45-277 nM) can be distinguished from a lower-affinity binding event (KD 666-1190 nM). This is direct evidence for multiple binding sites for gangliosides of the 1b series at TeNT as proposed by Emsley et al. [Emsley, Fotinou, Black, Fairweather, Charles, Watts, Hewitt and Isaacs (2000) J. Biol. Chem. 275, 8889-8894]. In agreement with previous reports, no binding was observed for gangliosides GM1, GM2, GM3 and GD2. The thermal denaturation of TeNT was characterized by two unfolding transitions centred around 57.4 and 62.4 degrees C. The conversion of TeNT into the toxoid form by formaldehyde treatment was accompanied by a large increase in Tm (the midpoint of protein unfolding transition, that is, the temperature at which half the protein is denatured and the other half is still present in its native form). Fetuin and asialofetuin bound to PT with similar affinities (KD 420 and 335 nM respectively). Binding was largely enthalpy-driven and counterbalanced by an unfavourable entropy change, indicating a loss of conformational flexibility. The latter could account for the observed inhibition of ATP binding after binding to fetuin. Furthermore, the molecular limits of mature PT subunit S5 were defined by MS and N-terminal peptide sequencing. The differential-scanning-calorimetry thermogram of FHA shows four well-resolved unfolding transitions, a finding consistent with the sequential denaturation of four structural domains.
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PMID:The use of microcalorimetry to characterize tetanus neurotoxin, pertussis toxin and filamentous haemagglutinin. 1291 36