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)

UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from [3H-nicotinamide]NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from [32P-adenylate]NAD (0.2 mol/mol of protein). Label from [3H-nicotinamide]NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with [3H-nicotinamide]NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.
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PMID:Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD. 280 35

Transducin is the substrate for a pertussis toxin-catalyzed ADP-ribosylation in isolated retinal rod disk membranes [(1984) J. Biol. Chem. 259, 23-26]. The effects of the toxin on the light responses of intact dark-adapted rods were studied. Applied close to a rod outer segment in a retinal slice, pertussis toxin depolarized the rod by a few millivolts and produced a long-lasting depression of light responses, effects which depended on penetration of toxin into rods. Nicotinamide, an inhibitor of ADP-ribosylation, not only blocked the action of the toxin, but also reversed the effects once established. The action of nicotinamide itself on rods indicates the presence of endogenous ADP-ribosyltransferases which may constitute a control system modulating phototransduction. Inhibition of phospholipase C by neomycin had only transient effects indicating that the cGMP, rather than a phosphoinositide, pathway is primary in vertebrate phototransduction. Rapid reversal of pertussis toxin action suggests possible clinical applications of nicotinamide or congeners to the treatment of disease caused by ADP-ribosylating bacterial toxins.
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PMID:Block of light responses of salamander rods by pertussis toxin and reversal by nicotinamide. 283 Oct 82

The heat-stable enterotoxin (STa) of E. coli activates intestinal guanylate cyclase and leads to increased cGMP levels by an as yet undetermined mechanism. In comparing this cGMP system to other known toxin-mediated alterations in cAMP metabolism, we observed that pertussis toxin caused lower levels of intestinal cGMP synthesis in response to purified STa. Another participant in ADP-ribosylation reactions, NAD, enhanced the ability of STa to activate guanylate cyclase, yet had no effect on basal enzyme activity. Niacinamide and isoniacinamide also had no effect on basal activity, but attenuated the STa activation. These results are discussed in relation to current models of hormone/toxin-sensitive adenylate cyclase, and may suggest an involvement of guanine-nucleotide-binding proteins in intestinal cGMP metabolism.
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PMID:Activation of guanylate cyclase by E. coli heat-stable enterotoxin (STa). Modulation by NAD and pertussis toxin. 287 59

[32P]ADP-ribosylation of membrane proteins catalyzed by either cholera toxin or pertussis toxin was markedly enhanced by NADP+. The effect was concentration dependent; with 20 microM [32P]NAD+ as a substrate maximal enhancement was obtained at a concentration of 0.5-1.0 mM NADP+ for rabbit and guinea-pig liver membranes and 0.1 mM NADP+ for human erythrocyte membranes. NADP+ appears to act by inhibiting the degradation of NAD+ by NAD+-glycohydrolase (NADase) present in membrane preparations, probably as an alternate substrate for the enzyme. Among inhibitors tested (NADP+, isonicotinic acid hydrazide, imidazole, nicotinamide, L-arginine methyl ester and HgCl2) to suppress the enzyme activity, NADP+ was the most effective and, at 10 mM, inhibited hepatic NADase activity by about 90%. The effect of NADP+ was much greater than that of other known effectors of ADP-ribosylation such as Mg2+ and phosphate, or the NADase inhibitors, isonicotinic acid hydrazide and isonicotinamide. In membranes which contain substantial activities of NADase the inclusion of NADP+ in the assay system is necessary to achieve maximal ADP-ribosylation of membrane proteins.
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PMID:NADP+ enhances cholera and pertussis toxin-catalyzed ADP-ribosylation of membrane proteins. 302 76

We previously have shown that alpha-adrenergic stimulation of canine Purkinje fibers and rat ventricle decreases automaticity. Experiments on rat ventricular myocytes in tissue culture have suggested that the decrease in automaticity induced by alpha-adrenergic stimulation depends on the development of sympathetic innervation and the presence of a pertussis toxin-sensitive, 41-kDa guanosine triphosphate (GTP)-regulatory protein. In the present study, microelectrode and biochemical techniques were used to test the role of the pertussis toxin-sensitive protein and sympathetic innervation in modulating automaticity of adult canine Purkinje fibers. Fibers were incubated in Tyrode's solution alone or in Tyrode's solution plus pertussis toxin (0.1-0.5 microgram/ml) for 24 hours and were then superfused with phenylephrine. Phenylephrine in the 5 x 10(-9)-5 x 10(-8) M range induced a decrease in automaticity in 63% of the 16 fibers not treated with pertussis toxin and an increase in automaticity in 37%. The former group had a higher level of pertussis toxin-sensitive substrate by the [32P]nicotinamide adenine dinucleotide adenosine diphosphate (ADP)-ribosylation assay than the latter. In contrast, all fibers treated with pertussis toxin (0.5 microgram/ml) showed increased automaticity in response to phenylephrine and had no detectable pertussis toxin-sensitive substrate. Over the range of pertussis toxin concentrations studied, there was a smooth concentration-response relation between the substrate levels measured and the automatic response to phenylephrine. As ADP-ribosylatable substrate levels decreased, the percent of fibers showing an increase in automaticity increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of a pertussis toxin-sensitive protein in the modulation of canine Purkinje fiber automaticity. 312 90

Nicotinamide 1,N6-ethenoadenine dinucleotide (etheno-NAD, epsilon-NAD), a fluorescent analogue of NAD, was able to serve as a substrate for the bacterial toxin-catalyzed epsilon-ADP ribosylation of signal-transducing G-proteins. Pertussis toxin and transducin were used as a model system to characterize this reaction. Similar to ADP ribosylation using NAD as substrate, the epsilon-ADP ribosylation occurs at the carboxyl-terminal 5-kDa tryptic fragment of the T alpha subunit of transducin with the same labeling stoichiometry; however, the rate of labeling is slightly slower. epsilon-NAD competes with NAD as a substrate which suggests that the epsilon-ADP ribosylation occurs at Cys-347 of the T alpha subunit. The biochemical effects of epsilon-ADP ribosylation on transducin are similar to those of ADP ribosylation and include inhibition of the GTPase and [3H]Gpp(NH)p-binding activities. The epsilon-ADP-ribosylated transducin exhibits a fluorescent spectrum which resembles that of epsilon-ADP with an excitation maximum at 292 nm and an emission maximum of 413 nm. Removal of the amino-terminal peptide of epsilon-ADP-ribosylated T alpha with either Staphylococcus aureus V8 protease or trypsin results in a decrease in the emission intensity. This result suggests that the amino- and carboxyl-terminal peptides of the T alpha molecule may interact with each other as suggested previously (Hingorani, V. N., and Ho, Y.-K. (1987) FEBS Lett. 220, 15-22). epsilon-NAD should prove to be a useful fluorescent substrate for future studies of the ADP ribosylation reaction in biological systems.
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PMID:Fluorescent labeling of signal-transducing G-proteins. Pertussis toxin-catalyzed etheno-ADP ribosylation of transducin. 314 31

We examined Bordetella avium for virulence factors common to Bordetella pertussis, including pertussis toxin, filamentous hemagglutinin, adenylate cyclase, dermonecrotic toxin, and tracheal cytotoxin. B. avium produced a dermonecrotic toxin and a tracheal cytotoxin. The dermonecrotic toxin of B. avium is a 155,000-molecular-weight, heat-labile protein which was lethal for mice, guinea pigs, young chickens, and turkey poults and produced dermonecrosis when injected intradermally into guinea pigs, chickens, and turkey poults. High-pressure liquid chromatography of B. avium culture supernatant fluid revealed the presence of a tracheal cytotoxin chemically identical to that produced by B. pertussis. B. avium isolates were negative for B. pertussis-like filamentous hemagglutinin and pertussis toxin when assayed with antibody against B. pertussis filamentous hemagglutinin and pertussis toxin. Furthermore, B. avium failed to induce the clustered CHO cell morphology characteristic of pertussis toxin. Adenylate cyclase assays indicated that B. avium does not produce an extracytoplasmic adenylate cyclase, even after passage through embryonated turkey eggs. Since production of virulence proteins by B. pertussis is regulated by growth in media containing nicotinamide or MgSO4 or by growth at reduced temperatures, we determined the effect of these supplements and growth conditions on production of dermonecrotic toxin by B. avium. Production of dermonecrotic toxin in B. avium was not altered by growth in media containing 100 microM FeSO4 or 500 micrograms of nicotinamide per ml or by growth at 25 or 42 degrees C, but production was significantly decreased by growth in media containing 20 mM MgSO4 and slightly reduced by growth in media containing 500 micrograms of nicotinic acid per ml. These studies revealed that B. avium is similar to B. pertussis in that both species produce a dermonecrotic toxin and a tracheal cytotoxin and production of dermonecrotic toxin is regulated by nicotinamide and MgSO4. The presence of dermonecrotic toxin and tracheal cytotoxin in all Bordetella species indicates that these products may be important virulence factors in bordetellosis.
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PMID:Dermonecrotic toxin and tracheal cytotoxin, putative virulence factors of Bordetella avium. 338 73

Cyclic adenosine 3',5'-monophosphate (cAMP) plays a critical role in modulating a variety of neuronal responses in Aplysia californica. Previous studies have focused on the neurotransmitter activation of adenylate cyclase, which presumably occurs via the guanosine 5'-triphosphate (GTP)-regulated excitatory subunit (Ns). While adenylate cyclase has also been shown to be regulated by inhibitory neurotransmitters, coupled through the inhibitory GTP-regulated coupling protein Ni in some systems, the effects of Ni-mediated adenylate cyclase inhibition on neuronal processing in Aplysia have not previously been reported. In the present study Ni is detected in Aplysia by both protein chemistry and enzymatic activity. A 40 kdalton substrate for the enzymatic activity of Bordetella pertussis toxin is observed. Incubation of Aplysia nervous tissue homogenates with pertussis toxin (IAP) and 32P-nicotinamide-adenine dinucleotide labels a single protein, assessed by polyacrylamide gel electrophoresis and autoradiography. Furthermore, crude membrane suspensions of this tissue demonstrate biphasic adenylate cyclase activity in response to increasing concentrations of GTP, showing Ni and Ns functional activities. These findings provide evidence that Ni is present in Aplysia tissue. Ni may serve as an important site for the regulation of cAMP synthesis and neuronal plasticity.
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PMID:Evidence for the inhibitory subunit of adenylate cyclase (Ni) in nervous and heart tissue of Aplysia. 396 Mar 97

Adrenergic mechanism for phosphorylase activation was gradually converted from an alpha 1- to a beta 2-type during primary culture of rat hepatocytes. beta 2-Receptor-mediated cAMP generation was also much greater in 8-h cultured cells than in fresh cells. Incubation of hepatocyte membranes with [alpha-32P]NAD and the preactivated A-protomer (an active component) of islet-activating protein (IAP), pertussis toxin, resulted in the ADP-ribosylation of a specific IAP substrate protein (Mr = 41,000). This ADP-ribosylation diminished progressively when the membrane-donor hepatocytes had been cultured. The early diminution was interfered with by the addition of nicotinamide or isonicotinamide, a potent inhibitor of ADP-ribosyltransferase, to the culture medium. The decrease of the IAP substrate was well correlated with the potentiation of beta-adrenergic functions under various conditions of culture. beta-Receptor-mediated activation of GTP-dependent membrane adenylate cyclase was, but glucagon-induced activation was not enhanced by either prior culture of hepatocytes or prior exposure of membranes to the A-protomer of IAP. There was no further enhancement, however, when membranes from cultured cells were exposed to the active toxin. Thus, the IAP-susceptible inhibitory guanine nucleotide-regulatory protein is coupled to beta-adrenergic receptors in such a manner as to reduce the degree of activation of cyclase, and the decrease in this IAP substrate may be responsible, at least partly, for development of beta-receptor functions during culture of hepatocytes. Its possible relation to accompanying inhibition of alpha 1-receptor functions is discussed.
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PMID:Conversion of adrenergic mechanism from an alpha- to a beta-type during primary culture of rat hepatocytes. Accompanying decreases in the function of the inhibitory guanine nucleotide regulatory component of adenylate cyclase identified as the substrate of islet-activating protein. 609 73

A solid, transparent culture medium for the study of the lytic spectrum of the phages, active against B. pertussis and B. bronchiseptica, in respect to homologous and heterologous bacteria of the genus Bordetella has been developed. The Cohen-Wheeler liquid medium with nicotinic acid and nicotinamide added, solidified with agar, is nicotinamide added, solidified with agar, is used as the base of the new medium. This base ensures the growth of B. parapertussis and B. bronchiseptica. To stimulate the growth of B. pertussis, the tissue stimulant of B. pertussis growth (a transparent substrate obtained from the tissue of the large intestine of a rabbit) has been used. With 10% of this stimulant added, B. pertussis cells have been found to preserve their typical morphological and immunobiological properties.
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PMID:[Transparent solid nutrient medium for studying the lytic spectrum of bacteriophages of microbes of the genus Bordetella]. 628 67


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