SEARCH · PubMed Health

Results for “toxin secretion system”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources

PubMed2000

Immunostimulatory sequence oligodeoxynucleotide: A novel mucosal adjuvant.

The majority of infectious agents enter the body via mucosal surfaces. Therefore, there is great interest in developing vaccination strategies that lead to mucosal immunity. However, to generate strong mucosal immune responses to nonreplicating immunogens, mucosal delivery with an adjuvant is required, and no safe and effective mucosal adjuvants are presently available for use in humans. Recently, immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) has been shown to be a potent mucosal adjuvant. Intranasal (i.n.) delivery of antigen with ISS-ODN elicits a secretory IgA response both locally in respiratory secretions and distally in intestinal and vaginal secretions. In this regard, ISS-ODN has been shown to be as effective as cholera toxin (CT), but unlike CT, ISS-ODN has not been shown to have significant toxicity. Furthermore, i.n. antigen/ISS-ODN coimmunization induces a strong Th(1)-biased systemic immune response with cytotoxic T lymphocyte activity. These observations suggest that ISS-ODN would be an ideal mucosal adjuvant for development of vaccines against mucosal pathogens.

Adjuvants, Immunologic↗

PubMed1964

OSTRACITOXIN: AN ICHTHYOTOXIC STRESS SECRETION OF THE BOXFISH, OSTRACION LENTIGINOSUS.

Boxfish under stress produce an ichthyotoxic, hemolytic, nonprotein poison in the mucous secretions of their skin. This heat-stable, nondialyzable "ostracitoxin" foams profusely in aqueous solutions and is toxic to various biological systems. It is apparently unique among known fish poisons; it is toxic to boxfish and resembles red tide and sea cucumber toxins in general properties.

Animals↗

PubMed1994

ADP ribosylation by cholera toxin identifies three G-proteins that are activated by the galanin receptor. Studies with RINm5F cell membranes.

Inhibition of insulin secretion by galanin is pertussis toxin (PTX) sensitive, suggesting the activation of one or more heterotrimeric (alpha, beta, gamma) G-proteins (Gi/Go). Multiple effectors, including the K+ATP and L-type Ca2+ channels, adenylyl cyclase, and an as yet unidentified system at a site close to exocytosis, are modulated by galanin. Therefore, it is necessary to delineate the particular G-proteins activated by the galanin receptor as a first step to understanding its net cellular response. During specific conditions, cholera toxin (CTX) can ADP-ribosylate the alpha i/alpha o-subunits of the PTX-sensitive substrates but only during receptor/G-protein interaction. Therefore, we used CTX-catalyzed ADP ribosylation to identify galanin receptor-associated G-protein alpha-subunits in RINm5F cells. Galanin enhanced the ADP ribosylation of membrane proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in two bands at 39,000 and 42,000 M(r). This labeling was blocked in membranes prepared from PTX-treated cells, enhanced by Mg2+, and showed a biphasic dependence on exogenous guanine nucleotides. Identification of the CTX ADP-ribosylated G-proteins by immunoprecipitation with selective antisera indicate activation by the galanin receptor of alpha i1 and alpha i3, which have the same mobility on SDS-PAGE (42,000 M(r)), and alpha i2 (39,000 M(r)). These studies provide evidence for the activation of multiple G-proteins by receptors for galanin in RINm5F cells.

Adenosine Diphosphate Ribose↗

PubMed1980

[New data on the mechanisms of the effect of cholera toxin].

Data from the literature on cholera pathogenesis in man and experimental animals are presented. The essence of secretion and filtration theories of rapid dehydration of the intestinal tract as well as that of the secretion-filtration theory proposed by the author are discussed. The data of both national and foreign authors are used in the discussion of the mechanisms of cholera toxin action. New observations on changes in the enzyme content (adenylate- and guanylate-cyclase systems) as well as the data on changes of the element composition of epithelial cells of different parts of the small intestine villi, on the role of local immunity in prevention of cholera toxicity are presented from the author's own observations and those of the laboratory staff members.

Adenylyl Cyclases↗

PubMed1984

Yeast killer toxin and an immunity protein are processed from a composite precursor.

Yeast killer toxin is a secreted protein that kills sensitive cells by forming an ion-conducting channel. The toxin is synthesized as a larger composite precursor containing two toxin subunits and an immunity protein. The processing and action of this precursor and its components provide an attractive system for studying these cellular events common to eukaryotes.

Amino Acid Sequence↗

PubMed1988

Effect of pertussis toxin and neomycin on G-protein-regulated polyphosphoinositide phosphodiesterase. A comparison between HL60 membranes and permeabilized HL60 cells.

The promyelocytic HL60 cell can be differentiated with dimethyl sulphoxide or dibutyryl cyclic AMP leading to the appearance of fMetLeuPhe receptors on the cell surface. G-protein-stimulated polyphosphoinositide phosphodiesterase (PPI-pde) activity was assessed in membranes prepared from both differentiated and non-differentiated HL60 cells. Both the extent of the response and the rank order of potency of the GTP analogues to stimulate PPI-pde activation (guanosine 5'-[gamma-thio]triphosphate (GTP[S]) greater than guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG) greater than guanosine 5'-[beta gamma-methylene]triphosphate (p[CH2]ppG) remains unchanged after differentiation with dimethyl sulphoxide. In comparison, differentiation by dibutyryl cyclic AMP leads to diminution of PPI-pde activity when stimulated by GTP[S] or fluoride, but not by millimolar concentrations of Ca2+. GTP[S]-stimulated PPI-pde in membranes is sensitive to the presence of Ca2+ (pCa 8-5). Pertussis-toxin pretreatment of intact HL60 cells leads to inhibition of both the secretory response and the formation of inositol phosphates when stimulated by fMetLeuPhe. In contrast, pertussis-toxin pretreatment has no effect on either GTP[S]- or fluoride-stimulated PPI-pde. Neomycin in a concentration-dependent manner inhibits both GTP[S] plus Ca2+ (pCa 5)-stimulated secretion and PPI-pde activation in streptolysin-O-permeabilized cells. The extent of PPI-pde activation in membranes compared with streptolysin-O-permeabilized cells reveals that the membrane preparation does not possess all the components that make up the inositide signalling system.

Calcium↗

PubMed1996

Lithium stimulation of rat pancreatic beta-cell replication is mediated through pertussis toxin-sensitive GTP-binding proteins and occurs independently of Ca2+ influx, cAMP, or protein kinase C activation.

We recently demonstrated the mitogenic and secretagogic actions of lithium in the insulin-producing pancreatic beta-cell (Sjöholm A, Welsh N, Hellerström C: Lithium increases DNA replication, polyamine content and insulin secretion by rat pancreatic beta-cells in vitro. Am J Physiol 262:C391-C395, 1992). In this study, the influence of lithium on beta-cell signal transduction pathways was monitored and their importance for the stimulated cell replication and hormone secretion was elucidated by selective pharmacological probes. To this end, fetal rat pancreatic islets enriched in beta-cells were isolated and cultured for 3 days with or without 10 mmol/l LiCl. This resulted in a marked mitogenic response by the beta-cells, of similar magnitude to that obtained by pharmacological activation of cAMP-dependent protein kinases by forskolin or the Sp-diastereomer of cAMP or protein kinase C stimulation by phorbol ester. However, neither did lithium affect the islet content of cAMP (whereas forskolin did), nor was the mitogenic response to the ion impeded when islets were pretreated with the Rp-diastereomer of cAMP, a specific antagonist of cAMP-dependent protein kinases, or by the Ca2+ channel blocker D-600. The protein kinase C inhibitor 1-(5'-isoquinolinesulfonyl)-2-methylpiperazine prevented the mitogenicity of phorbol ester, but not that of lithium. Conversely, addition of increasing concentrations of inositol along with lithium also did not affect the mitogenicity of the ion, providing indirect evidence against the involvement of protein kinase C in mediating the growth-promoting effect of lithium in this system. It was found that pretreatment of islets with pertussis toxin, which inactivates GTP-binding proteins by ADP-ribosylation, prevented the mitogenicity and part of the secretagogic action of lithium. It is concluded that although specific activation of the cAMP and protein kinase C signaling systems appears sufficient to trigger a mitogenic response of the beta-cell, lithium seemingly does not work through any of these systems nor via Ca2+ influx in promoting beta-cell mitogenesis. Our results, moreover, suggest that the actions of lithium are conveyed by pertussis toxin-sensitive GTP-binding proteins.

Animals↗

PubMed1992

Construction and expression of diphtheria toxin-encoding gene derivatives in Escherichia coli.

We reported earlier that in the periplasmic space of Escherichia coli, truncated derivatives of diphtheria toxin undergo limited proteolysis [Zdanovsky et al., Mol. Biol. 22 (1988) 1037-1293]. Here, we present data indicating that this proteolysis is reduced in cells bearing a mutation in the degP gene. We have also constructed hybrid genes whose products are not secreted into the periplasm. These hybrid genes were expressed in E. coli from both the pR promoter, controlled by the heat-inducible CI857 repressor, and from the P(lac) promoter, controlled by the IPTG-inducible LacI repressor. The latter system proved to be more productive.

Bacteriophage lambda↗

PubMed2000

Prevention of yeast spoilage in feed and food by the yeast mycocin HMK.

The yeast Williopsis mrakii produces a mycocin or yeast killer toxin designated HMK; this toxin exhibits high thermal stability, high pH stability, and a broad spectrum of activity against other yeasts. We describe construction of a synthetic gene for mycocin HMK and heterologous expression of this toxin in Aspergillus niger. Mycocin HMK was fused to a glucoamylase protein carrier, which resulted in secretion of biologically active mycocin into the culture media. A partial purification protocol was developed, and a comparison with native W. mrakii mycocin showed that the heterologously expressed mycocin had similar physiological properties and an almost identical spectrum of biological activity against a number of yeasts isolated from silage and yoghurt. Two food and feed production systems prone to yeast spoilage were used as models to assess the ability of mycocin HMK to act as a biocontrol agent. The onset of aerobic spoilage in mature maize silage was delayed by application of A. niger mycocin HMK on opening because the toxin inhibited growth of the indigenous spoilage yeasts. This helped maintain both higher lactic acid levels and a lower pH. In yoghurt spiked with dairy spoilage yeasts, A. niger mycocin HMK was active at all of the storage temperatures tested at which yeast growth occurred, and there was no resurgence of resistant yeasts. The higher the yeast growth rate, the more effective the killing action of the mycocin. Thus, mycocin HMK has potential applications in controlling both silage spoilage and yoghurt spoilage caused by yeasts.

Aerobiosis↗

PubMed1998

Enteric infections in an endemic area induce a circulating antibody-secreting cell response with homing potentials to both mucosal and systemic tissues.

Enteric infections induce a response of circulating pathogen-specific antibody-secreting cells (ASC). The expression of homing receptors (HRs) on these cells was studied in patients with diarrhea caused by Vibrio cholerae in Bangladesh, an area in which cholera is endemic. The gut HR, alpha4beta7, was expressed by approximately 80% of the ASC, indicating mucosal homing of these cells. However, the peripheral lymph node HR, L-selectin, was also expressed by approximately 80% of the ASC specific to either cholera toxin or O antigen. In earlier findings after oral immunization in nonendemic areas, alpha4beta7 has been expressed by approximately 100% and L-selectin by approximately 50% of the ASC. In comparison, the present data speak for a more systemic targeting of the immune response associated with long-lasting immunity in an endemic area. The results thus provide insight for the continued development and evaluation of vaccines.

Adolescent↗

PubMed2005

Stable episomal expression system under control of a stress inducible promoter enhances the immunogenicity of Bacillus subtilis as a vector for antigen delivery.

Bacillus subtilis has been successfully engineered to express heterologous antigens genetically fused to surface-exposed spore coat proteins as a vaccine vehicle endowed with remarkable heat resistance and probiotic effects for both humans and animals. Nonetheless, the immunogenicity of passenger antigens expressed by B. subtilis spores is low particularly following oral delivery. In this work, we describe a new episomal expression system promoting enhanced immunogenicity of heterologous antigens carried by B. subtilis strains, either in the form of spores or vegetative cells, following oral or parenteral delivery to mice. Based on a bi-directional replicating multicopy plasmid, the gene encoding the B subunit of the heat-labile toxin (LTB), produced by enterotoxigenic Escherichia coli (ETEC) strains, was cloned under the control of the B. subtilis glucose starvation inducible (gsiB) gene promoter, active in vegetative cells submitted to heat and other stress conditions. The recombinant plasmid proved to be structurally and segregationally stable in both cells and spores under in vitro and in vivo conditions. Moreover, BALB/c mice orally immunized with B. subtilis cells or spores elicited enhanced anti-LTB systemic (serum IgG) and secreted (fecal IgA) antibody responses, thus, suggesting that antigen expression occurred during in vivo transit. These results indicate that the new episomal expression system may improve the performance of B. subtilis as a live orally-delivered vaccine carrier.

Administration, Oral↗

PubMedDate not supplied

Toxin resistance and reduced secretion in a mouse L-cell mutant defective in herpes virus propagation.

The mouse L-cell mutant gro29 was selected originally for its inability to propagate herpes simplex virus; it shows severe defects in virus egress and the transport and processing of viral glycoproteins after infection. In this report, we show that uninfected gro29 cells display pleiotropic changes in protein secretion, oligosaccharide processing, and sensitivity to the toxins ricin and modeccin. Specifically, the rate of secretion of a nonglycosylated protein, human growth hormone, was reduced 70% in gro29 cells compared with the parental L cells. A direct measurement of the transport capacity of Golgi membranes in a cell-free assay suggests that gro29 cells contain less functional Golgi than parental cells. Despite this deficiency, N-linked oligosaccharides were processed efficiently in mutant cells, although there were differences in the structure of the mature forms. Lectin intoxication assays revealed that gro29 cells were cross-resistant to killing by the cytotoxic lectins ricin and modeccin, but not to wheat germ agglutinin, Ricinus communis agglutinin RCA120, or leucoagglutinin. Fluorescence labeling using fluorescein-conjugated lectins showed that uninfected gro29 cells expressed relatively few ricin-binding molecules, suggesting a possible mechanism for toxin resistance. These studies provide evidence that the processes of protein secretion, lectin intoxication, and herpes virus maturation and egress may share a common cellular component.

Animals↗

PubMed1983

Bicarbonate transport across the frog choroid plexus and its control by cyclic nucleotides.

We have studied the effects of ions, hormones, diuretics and cyclic nucleotides on the short-circuit current (Isc) across the frog choroid plexus. In normal HCO3 Ringer solution, the trans-epithelial potential difference (p.d.), Isc and resistance (Rt) were -0.8 mV (ventricular side negative with respect to to the blood (serosal) side), 6 microA/cm2 and 170 omega cm2, respectively. Removal of Na, Cl or HCO3 from the solution decreased the Isc to 1.9, 2.3 or -4.6 microA/cm2, respectively. Theophylline, dibutyryl cyclic AMP, isoproterenol, prostaglandin E1, ACTH, cholera toxin and forskolin all significantly increased the Isc. The theophylline-induced change in Isc (delta Itheosc) was reduced by 50% upon Cl substitution with gluconate, and was abolished to less than 12% by Na-free and HCO3-free solutions. pH monitoring of the bathing solutions showed that acidification of the serosal bathing fluid was enhanced by theophylline while that of the ventricular solution was retarded. Ouabain, acetazolamide, SITS, DIDS and furosemide inhibited both Isc and delta Itheosc. We conclude that HCO3 secretion by the choroid plexus into the c.s.f. is controlled by hormones which stimulate the adenylate cyclase system, and propose a model of ion transport across the choroidal epithelium.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1997

Relationships between dopamine-induced changes in cytosolic free calcium concentration ([Ca2+]i) and rate of prolactin secretion. Elevated [Ca2+]i does not indicate prolactin release.

This study was undertaken to investigate the relationship between dopamine (DA) induced changes in the cytosolic calcium concentration ([Ca2+]i) and the rate of prolactin secretion using GH4ZR7, a rat pituitary cell line, which express only one subtype of D2 receptor. GH4ZR7 cells were loaded with Fluo-3, a fluorescent Ca2+ indicator, and then perifused with two different doses of DA (10(-7) mol/L and 5 x 10(-4) mol/L). We monitored changes in [Ca2+]i and rate of prolactin release simultaneously by attaching a spectrofluorometer to a dynamic perifusion system. DA has stimulatory and inhibitory effect on prolactin secretion in GH4ZR7 cells; 10(-7) mol/LDA slightly increased [Ca2+]i and stimulated prolactin release, whereas 5 x 10(-4) mol/LDA decreased [Ca2+]i and inhibited prolactin secretion. When the cells were pretreated with pertussis toxin (PTX), 10(-7) mol/L DA had no significant change in [Ca2+]i while stimulating prolactin release, and 5 x 10(-4) mol/L DA reduced [Ca2+]i without having any significant effect on the rate of prolactin secretion. The results of this study demonstrate that changes in [Ca2+]i do not always correlate with the rate of prolactin release from lactotrophs. The dissociation between [Ca2+]i and prolactin release is somewhat expected considering the diverse role of [Ca2+]i and post-[Ca2+]i events, which can change the rate of prolactin release.

Aniline Compounds↗

PubMed1989

Nitroimidazole derivatives inhibit anterior pituitary cell function apparently by a direct effect on the catalytic subunit of the adenylate cyclase holoenzyme.

Nitroimidazole derivatives dose-dependently decreased basal and CRF-stimulated ACTH release, basal and GRF-stimulated rat GH release, and basal rat PRL release in primary cultures of rat anterior pituitary cells. In addition, basal and CRF-stimulated mRNA coding for the ACTH precursor were reduced after preincubation with the nitroimidazole derivatives. Miconazole, econazole, isoconazole, clotrimazole, and bifonazole had similar or more pronounced effects on anterior pituitary function compared to ketoconazole, whereas metronidazole and etomidate were less effective. The positive correlation between the number of phenylated side-chains or phenolic rings of the imidazole molecule and the efficacy to inhibit activity on pituitary hormone secretion suggests a structure-activity relationship of these compounds. The effects of the nitroimidazole derivatives on anterior pituitary hormone release and biosynthesis were mediated by cAMP. Thus, basal and CRF-, cholera toxin-, and forskolin-stimulated adenylate cyclase activities in rat anterior pituitary cell membranes determined by cAMP formation were suppressed by the nitroimidazole derivatives. Pertussis toxin did not diminish the nitroimidazole derivative effect on cAMP formation. The adenylate cyclase inhibitory effect of these substances was independent of the presence of GTP in the assay system, underlining a direct effect on the catalytic subunit. In addition, basal and forskolin-stimulated cAMP generation in membranes of S49 lymphoma cyc-variants, which lack a functional Gs protein, was efficiently suppressed (by up to 90%) by the nitroimidazole derivatives. In conclusion, ketoconazole and other nitroimidazole derivatives inhibit anterior pituitary hormone synthesis and secretion apparently by a direct effect on the catalytic subunit of the adenylate cyclase system.

Adenylyl Cyclase Inhibitors↗

PubMedDate not supplied

[Renal osteodystrophy (I)].

Renal bone disease represents one of the major complications of end-stage renal disease, accounting for the numerous and various changes at bone level, determined by abnormal calcium and phosphorus homeostasis and by changes in calcitriol and PTH synthesis. PTH represents as well a major uraemic toxin, exerting profound systemic effects, particularly at the cardiovascular level. PTH synthesis is mainly controlled by changes in calcium-phosphorus balance and calcitriol production by the kidneys. Several others factors are important in the development of secondary hyperparathyroidism: acidosis, autonomisation of PTH secretion and peripheral (target-organ) resistance to PTH actions. Although bone biopsy represents the definitive diagnostic test to differentiate between osteitis fibrosa, low-turnover bone disease and bone involvement unrelated to disturbed calcium metabolism (i.e. beta 2-microglobulin-related amyloidosis), plasma intact PTH generally exhibits a reasonably good relation with bone histology parameters. Moreover serum bone-specific alkaline phosphatase isoenzyme, serum pyridinoline and the novel serum markers for bone turnover are highly specific and correlate with bone histomorphometry parameters, so that, preventive and therapeutic strategies should be re-evaluated based solely on biochemical parameters.

Alkaline Phosphatase↗

PubMedDate not supplied

[Renal osteodystrophy(II)].

Chronic Kidney Disease-Mineral and Bone Disorder↗

PubMedDate not supplied

Characterization of the mucosal immune response to 2-acetylaminofluorene-protein conjugates.

Many environmental carcinogens gain access to the body only after traversing a mucosal surface. Due to their small size, most carcinogens are not recognized by the immune system and pass unhindered from the external to the internal environment. In previous studies, we demonstrated that secretory IgA directed against the carcinogen 2-acetylaminofluorene (AAF) can be elicited by covalently coupling AAF to the mucosal immunogen cholera toxin (CT). Rabbit intestines receiving secretions containing secretory IgA anti-AAF demonstrated a marked reduction in transmucosal absorption of carcinogen from the intestinal lumen to the mesenteric blood supply. In actively immune animals, however, recent data suggests that the disposition of luminal carcinogen may be influenced by the relative abundance of serum versus mucosally-based immunoglobulins. Our objective was to quantify the amount and isotype distribution of antibodies produced in response to AAF-carrier protein conjugates administered via different routes; using traditional parenteral carrier proteins and routes of administration, compared to mucosal carrier proteins and routes of administration. Administration of AAF-cholera toxin conjugates to isolated ileal (Thiry-Vella) loops in rabbits elicited a vigorous sIgA anti-AAF response in ileal secretions, with low levels of serum or intestinal IgG, or serum-based IgA produced concomitantly. All parenteral immunization protocols generated extremely high titers of serum IgG anti-AAF, with only moderate levels of sIgA produced concomitantly, even when mucosal boosting followed parenteral priming. When AAF-CT mucosal boosts were administered after intraperitoneal priming, a dramatic rise in serum, not secretory IgA was observed.

2-Acetylaminofluorene↗