Helicobacter pyloricytotoxin VacA increases alkaline secretion in gastric epithelial cells

2001 ◽  
Vol 281 (6) ◽  
pp. G1440-G1448 ◽  
Author(s):  
Lucantonio Debellis ◽  
Emanuele Papini ◽  
Rosa Caroppo ◽  
Cesare Montecucco ◽  
Silvana Curci
Keyword(s):  
Apical Membrane ◽  
Acid Output ◽  
Human Infection ◽  
Gastric Epithelium ◽  
Secondary Development ◽  
Acute Effects ◽  
Gastric Diseases ◽  
Gastric Glands ◽  
Frog Stomach ◽  
Alkaline Secretion

Human infection by the bacterium Helicobacter pylori (Hp) may lead to severe gastric diseases by an ill-understood process involving several virulence factors. Among these, the cytotoxin VacA is associated with higher tissue damage. In this study, the isolated frog stomach model was used to characterize the acute effects of VacA on the gastric epithelium. Our results show that VacA partially inhibits gastric acid output by increasing HCO[Formula: see text] efflux. Experiments conducted with double-barrelled pH or Cl−-selective microelectrodes on surface epithelial gastric cells (SECs) and single gastric glands show that VacA does not impair the activity of the oxyntic cells but renders the apical membrane of SECs more permeable to HCO[Formula: see text] and Cl−. Inhibition of this permeation by 5-nitro-2-(3-phenylpropylamino) benzoic acid indicates that this may be due to the formation of anion-selective pores by the toxin. We suggest that VacA-dependent HCO[Formula: see text] efflux from SECs improves the environmental conditions (pH, CO2concentration) of the niche parasitized by Hp, that is the gastric surface. This may favor Hp persistence in the tissue and the secondary development of a chronic inflammation.

scholarly journals Helicobacter Pylori Induce Gastric Upset

2021 ◽  
pp. 1-1
Author(s):  
Hazim Abdul Rahman Alhit
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Serum Antibody ◽  
Endoscopic Biopsy ◽  
Helicobacter Pylori Infection ◽  
Gastric Epithelium ◽  
Gastric Diseases ◽  
Heterogeneous Distribution ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

Editorial: Helicobacter pylori is a micro-aerophilic, helical-form gramnegative aggressive bacteria. Accordingly, the idiom “Helico” intimates its helical appearance, “bacter” symbolizes bacteria, while “pylori” denotes stomach due to the first and common site of this bacteria living. Further, Marshall B. and Warren R. observed and described it in 1982. Then, the followed investigators studied this bacterium in detail with its consequences and complexities [1]. Gastric upset (Indigestion), dyspepsia: means impaired gastric digestion. Accordingly, the patient complains of upper abdominal pain, heartburn, belching, nausea, even feeling earlier gastric fullness than expected while eating. Furthermore, there are many causes of indigestion like gastroesophageal reflux disease, ulcer disease, gastritis, and even gastric cancer. Hence, unexplained recent onset dyspepsia in older people may need additional examinations. Moreover, one of the common causes is Helicobacter pylori infection, which needs laboratory and endoscopic examination [2]. Argument Many theories investigated the etiology and pathogenesis of Helicobacter pylori infection, concerning chronic or acute gastritis. Hence, gastric upset is the main presentation of both types of gastritis. Evidences The genotype is valuable in determining the dominant Helicobacter pylori strains as the isolates were different genetically plus heterogeneous distribution. Accordingly, the vac and cag markers operate a significant function in defining clinical consequences. These virulence agents are present in a subset of Helicobacter pylori strains isolates like cagA, iceA, vacA, and ureC. Moreover, the cagA causes cytotoxins induction by the gastric epithelial cell as Interleukin 8 [3]. The molecular intercommunication researches exhibit that the act of acarus calamus in hindering biofilm formation in Helicobacter pylori is due to the inhibitory impact of phytobio-active component, β-sitosterol, on the quorum sensing molecules-ToxB, PhnB, DnaA, plus Sip. Consequently, this opinion may suggest the molecular mechanism of Helicobacter pylori in producing the acidrelated complaints and gives a clue to a new therapy [4]. Helicobacter pylori infection causes lncRNA risk impression linked to H. pylori in gastric cancer patients and can prognosticate the prediction of these patients [5]. There was a close relationship between raised serum IgE levels in Helicobacter pylori infected patients [6]. Counterargument The laboratory investigations of Helicobacter pylori infection depend on several factors like the fluctuations of serum antibody titers in a time series, the antigene detection in stool tests, the false-positive results of lab tests, or the manner of endoscopic biopsy collection. Furthermore, other factors like the variations in Cytotoxin-Associated Gene A (CagA) in East Asian patients. Moreover, the gastric nodularity or atrophy, the patient’s age, the severity of the gastric mucosal infection are causes of variations in Helicobacter pylori detection at the time of the investigation [7]. Refutation The significant markers of H. pylori, the presence of the vacuolating cytotoxin (vacA), the cytotoxin-associated gene A (cagA), which induced by the direct communication with gastric epithelium factor antigen (iceA gene), and the presence of urease C gene (ureC). Consequently, all these factors play the principal factors in deciding the gastric consequences of Helicobacter infections. Conclusion Helicobacter pylori induce gastric upset by several mechanisms to form numerous Gastric diseases.

On the pathology of gastric secretion of the peasant population

1930 ◽  
Vol 26 (12) ◽  
pp. 1190-1194
Author(s):  
V. E. Rodionov
Keyword(s):  
Gastric Secretion ◽  
Gastric Juice ◽  
Motor Function ◽  
Laboratory Data ◽  
The State ◽  
Objective Data ◽  
Gastric Diseases ◽  
Gastric Glands ◽  
Chemical Studies ◽  
Physiological Structure

As you know, the majority of gastric suffering is based on the pathology of the secretory and motor function of the stomach, depending or without it on the organic changes in its anatomical and physiological structure. In the presence of a complex of anamnestic and objective data, the state of secretion in each given case is laid on the basis for the diagnosis of gastric diseases, why the laboratory data in connection with the clinic serve as the starting material in our article. We took the result of chemical studies of gastric juice carried out in the Ardatov laboratory for 10 years from 1919 to 1928 inclusive in the amount of 2277 cases. We believe that this material is sufficient to reveal some aspects of the pathology of the function of the gastric glands depending on the conditions of nutrition and life of the peasant population, especially since in relation to nutrition during this period of time the population was in very different conditions.

Demonstration of a functional apical sodium hydrogen exchanger in isolated rat gastric glands

2003 ◽  
Vol 285 (6) ◽  
pp. G1242-G1248 ◽  
Author(s):  
Philipp Kirchhoff ◽  
Carsten A. Wagner ◽  
Florian Gaetzschmann ◽  
Klaus Radebold ◽  
John P. Geibel
Keyword(s):  
Apical Membrane ◽  
Specific Inhibitor ◽  
Parietal Cells ◽  
Proton Extrusion ◽  
Gastric Glands ◽  
Functional Studies ◽  
Sodium Hydrogen ◽  
Low Concentrations ◽  
Sodium Hydrogen Exchanger ◽  
Nhe Isoforms

Previous studies have shown that gastric glands express at least sodium-hydrogen exchanger (NHE) isoforms 1-4. Our aim was to study NHE-3 localization in rat parietal cells and to investigate the functional activity of an apical membrane NHE-3 isoform in parietal cells of rats. Western blot analysis and immunohistochemistry showed expression of NHE-3 in rat stomach colocalizing the protein in parietal cells together with the β-subunit of the H+-K+-ATPase. Functional studies in luminally perfused gastric glands demonstrated the presence of an apical NHE isoform sensitive to low concentrations of 5-ethylisopropyl amiloride (EIPA). Intracellular pH measurements in parietal cells conducted in omeprazole-pretreated superfused gastric glands showed an Na+-dependent proton extrusion pathway that was inhibited both by low concentrations of EIPA and by the NHE-3 specific inhibitor S3226. This pathway for proton extrusion had a higher activity in resting glands and was inhibited on stimulation of histamine-induced H+-K+-ATPase proton extrusion. We conclude that the NHE-3 isoform located on the apical membrane of parietal cells offers an additional pathway for proton secretion under resting conditions. Furthermore, the gastric NHE-3 appears to work under resting conditions and inactivates during periods of H+-K+-ATPase activity.

Protection against ethanol injury in the canine stomach: role of mucosal glutathione

1991 ◽  
Vol 261 (6) ◽  
pp. G966-G973 ◽  
Author(s):  
B. E. Victor ◽  
K. L. Schmidt ◽  
G. S. Smith ◽  
T. A. Miller
Keyword(s):  
Gastric Gland ◽  
Ethanol Exposure ◽  
Gastric Epithelium ◽  
Gastric Injury ◽  
Protective Effects ◽  
Experimental Conditions ◽  
Gastric Glands ◽  
The Status ◽  
Mild Irritant

The present study determined the role that mucosal glutathione (GSH) levels play in mediating the protective effects of a prostaglandin and a mild irritant against alcohol-induced gastric injury. An in vivo canine chambered stomach preparation was used in which the exteriorized mucosa was partitioned into two equal halves, one serving as control. Animals (5-8/group) received a subcutaneous injection of either normal saline (NS) or the GSH depletor N-ethylmaleimide (NEM; 50 mg/kg) and then were assigned to one of a variety of groups based on the perfusate used to bathe the experimental side of the chamber; NS bathed the control mucosa. At completion of the studies, mucosa from each side of the chamber was assayed for total GSH (mumol/g wet wt) and evaluated for microscopic damage. Both 16,16-dimethyl prostaglandin E2 (PGE2) (1 microgram/ml) and the mild irritant 8% ethanol, when topically applied to the gastric epithelium, increased mucosal GSH levels by approximately 20% compared with control values, and elicited no deleterious effects to the mucosa. Treatment of animals with NEM prevented these GSH effects by PGE2 and 8% ethanol without damaging the mucosa. Application of 40% ethanol to the mucosa markedly reduced levels of GSH and caused significant injury to the mucosal surface, much of it extending to the level of the gastric glands. When mucosa was pretreated with PGE2 or 8% ethanol before 40% ethanol exposure, deep gastric gland injury was virtually abolished. In animals receiving NEM, the protective effects of these agents against injury by 40% ethanol were prevented. Perturbations in tissue levels of GSH under these various experimental conditions failed to correlate histologically with the status of gastric mucosal integrity.

scholarly journals Cholesteryl α-D-glucoside 6-acyltransferase enhances the adhesion of Helicobacter pylori to gastric epithelium

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Hau-Ming Jan ◽  
Yi-Chi Chen ◽  
Tsai-Chen Yang ◽  
Lih-Lih Ong ◽  
Chia-Chen Chang ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Adhesion ◽  
Direct Synthesis ◽  
Membrane Vesicles ◽  
Etiologic Agent ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Gastric Diseases ◽  
Host Cell Membranes

AbstractHelicobacter pylori, the most common etiologic agent of gastric diseases including gastric cancer, is auxotrophic for cholesterol and has to hijack it from gastric epithelia. Upon uptake, the bacteria convert cholesterol to cholesteryl 6′-O-acyl-α-D-glucopyranoside (CAG) to promote lipid raft clustering in the host cell membranes. However, how CAG appears in the host to exert the pathogenesis still remains ambiguous. Herein we identified hp0499 to be the gene of cholesteryl α-D-glucopyranoside acyltransferase (CGAT). Together with cholesteryl glucosyltransferase (catalyzing the prior step), CGAT is secreted via outer membrane vesicles to the host cells for direct synthesis of CAG. This significantly enhances lipid rafts clustering, gathers adhesion molecules (including Lewis antigens and integrins α5, β1), and promotes more bacterial adhesion. Furthermore, the clinically used drug amiodarone was shown as a potent inhibitor of CGAT to effectively reduce the bacterial adhesion, indicating that CGAT is a potential target of therapeutic intervention.

Characterization of an 80-kDa phosphoprotein involved in parietal cell stimulation

1989 ◽  
Vol 256 (6) ◽  
pp. G1070-G1081 ◽  
Author(s):  
T. Urushidani ◽  
D. K. Hanzel ◽  
J. G. Forte
Keyword(s):  
Membrane Protein ◽  
Parietal Cell ◽  
Apical Membrane ◽  
Peptide Mapping ◽  
Integral Membrane Protein ◽  
Gastric Glands ◽  
Low Speed ◽  
Calcium Dependent ◽  
Apical Membranes

When isolated rabbit gastric glands were stimulated with histamine plus isobutylmethylxanthine, a redistribution of H+-K+-ATPase, from microsomes to a low-speed pellet, occurred in association with the phosphorylation of an 80-kDa protein (80K) in the apical membrane-rich fraction purified from the low-speed pellet. Histamine alone or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), but not carbachol, also stimulated both the redistribution of H+-K+-ATPase and phosphorylation of 80K. Under stimulated conditions, 80K copurified in the apical membrane fraction along with H+-K+-ATPase and actin; whereas purified microsomes from resting stomach were highly enriched in H+-K+-ATPase but contained neither 80K nor actin. Treatment of the apical membranes with detergents, salts, sonication, and so on, led us to conclude that 80K is a membrane protein, unlike actin; however, the mode of association of 80K with membrane differed from H+-K+-ATPase, an integral membrane protein. Isoelectric focusing and peptide mapping revealed that 80K consists of six isomers of slightly differing pI, with 32P occurring only in the three most acidic isomers and exclusively on serine residues. Moreover, stimulation elicited a shift in the amount of 80K isomers, from basic to acidic, as well as phosphorylation. We conclude that 80K is an apical membrane protein in the parietal cell and an important substrate for cAMP-dependent, but not calcium-dependent, pathway of acid secretion.

Anomalous potential difference responses to changes in sodium concentration in the antrum of frog stomach

1983 ◽  
Vol 245 (4) ◽  
pp. G554-G561 ◽  
Author(s):  
G. Carrasquer ◽  
D. Kissel ◽  
W. S. Rehm ◽  
M. Schwartz
Keyword(s):  
Rana Catesbeiana ◽  
Apical Membrane ◽  
Sodium Concentration ◽  
Potential Difference ◽  
Conductive Pathway ◽  
Luminal Side ◽  
Frog Stomach ◽  
Conductance Ratio ◽  
Cl Conductance

Previously, an electrogenic Na-Cl symport was found in the fundus, and the question arises of whether there is one in the antrum, a tissue that does not secrete acid. In an in vitro preparation of the antrum of Rana catesbeiana, we found that when the [Na+] in nutrient solution was decreased (choline for Na+) the transmucosal potential difference (PD) decreased (the positivity of nutrient side decreased), and when the [Na+] was increased the PD increased. These PD changes were anomalous for Na+ but not for choline. A linear relationship for PD versus log [Na+] and not versus log [choline] excluded a choline conductive pathway. The anomalous PD response was decreased but not abolished by 10(-3) M ouabain. Normal PD responses resulted from [Na+] changes in Cl--free (SO2-4) solutions. PD responses to changes in nutrient [Cl-] were normal but decreased in the absence of Na+. Data are compatible with a passive electrogenic Na-Cl symport with more chloride than sodium ions transported per cycle, as in the fundus. Symport conductance-to-total Cl- conductance ratio is higher in antrum than in the fundus. Data from the luminal side were compatible with apical membrane conductances for Na+ and Cl-.

Direct measurement of extracellular proton flux from isolated gastric glands

1994 ◽  
Vol 267 (5) ◽  
pp. C1473-C1482 ◽  
Author(s):  
A. Thibodeau ◽  
R. C. Kuo ◽  
J. M. Crothers ◽  
X. Yao ◽  
J. C. Owicki ◽  
...  
Keyword(s):  
Steady State ◽  
Apical Membrane ◽  
Ph Sensor ◽  
Disulfonic Acid ◽  
Sodium Thiocyanate ◽  
Weak Base ◽  
Extracellular Acidification ◽  
Gastric Glands ◽  
Isolated Gastric Glands ◽  
Short Circuits

We used the microphysiometer, a sensitive extracellular pH sensor, to resolve luminal (or apical) H+ secretion and basolateral release of OH- as well as liberation of acidic metabolites in rabbit gastric glands. Stimulation of glands via the adenosine 3',5'-cyclic monophosphate pathway produced a biphasic change in the extracellular acidification rate (EAR): after an initial transient decrease below the unstimulated baseline (-40.9 +/- 3.4%), the EAR increased to a steady-state maximal plateau (+98.1 +/- 5.3%) within 30 min (n = 37). We interpret the biphasic EAR profile as an initial excess of basolaterally released OH- followed by delayed luminal efflux of simultaneously produced H+. The elevated EAR at steady state reflected liberation of metabolic acid attributed to H(+)-K(+)-ATPase enzymatic activity. The presence of H2-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid prevented OH- release and reduced steady-state EAR. Basolateral OH- release and steady-state EAR were also inhibited by the H(+)-K(+)-ATPase inactivators omeprazole and SCH-28080. Inhibition of Na+/H+ exchange did not reduce steady-state EAR and did not affect apical H+ production, as judged by the accumulation of the weak base aminopyrine. Sodium thiocyanate (1 mM), which short circuits intraluminal H+ accumulation, blocked OH- release, demonstrating its dependence on H(+)-OH- separation at the apical membrane. A computerized model was developed to illustrate how the observed biphasic EAR profile would result from a delayed luminal efflux of H+ due to transitory intraluminal compartmentalization.

scholarly journals Alkaline secretion by frog gastric glands measured with pH microelectrodes in the gland lumen

1998 ◽  
Vol 513 (1) ◽  
pp. 235-241 ◽  
Author(s):  
Lucantonio Debellis ◽  
Rosa Caroppo ◽  
Eberhard Frömter ◽  
Silvana Curci
Keyword(s):  
Gastric Glands ◽  
Alkaline Secretion ◽  
Ph Microelectrodes

scholarly journals Effect of Purified Lipopolysaccharides from Strains of Helicobacter pylori and Helicobacter felis on Acid Secretion in Mouse Gastric Glands In Vitro

2001 ◽  
Vol 69 (6) ◽  
pp. 3891-3896 ◽  
Author(s):  
Ireneusz T. Padol ◽  
Anthony P. Moran ◽  
Richard H. Hunt
Keyword(s):  
Helicobacter Pylori ◽  
Acid Secretion ◽  
Acid Output ◽  
Prostaglandin E ◽  
Gastric Glands ◽  
Helicobacter Felis ◽  
Bacterial Pathogenicity ◽  
Close Proximity ◽  
H Pylori

ABSTRACT As a bacterial product, Helicobacter pylorilipopolysaccharide (LPS) can originate in close proximity to parietal cells, but the role of this uniquely structured endotoxin on acid secretion has not been fully investigated and remains unclear. The purpose of this study was to test the direct effect of purified LPS (tested range, 0.1 to 100 μg/ml) from various strains of H. pylori and from one Helicobacter felis strain on histamine- and carbachol-stimulated acid secretion in vitro using mouse gastric glands and the accumulation of [14C]aminopyrine. In addition, we investigated whether H. pylori LPS can interfere with two native antisecretory substances, prostaglandin E2 (PGE2) and somatostatin, which may contribute to bacterial pathogenicity. Except for the LPS from H. pylori SS1 (Sydney strain), which gave a statistically significant increase in both histamine- and carbachol-stimulated acid output (38 and 24%, respectively; P < 0.05), no effect of the tested LPS was observed on acid secretion. H. pylori LPS purified from a patient isolate did not affect the potency or the efficacy of the inhibitory dose response curve to PGE2 or somatostatin. Bacterial interstrain variation in the direct stimulatory effect of Helicobacter-derived LPS on acid secretion was observed, which probably reflects the molecular structure of LPS and the potential to contribute to virulence. Importantly, the data showed that H. pylori LPS did not have any direct antisecretory properties. It can be speculated that the acid stimulatory properties of LPS from H. pylori SS1 may contribute to the gastric damage observed in the mouse model ofH. pylori infection.

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