scholarly journals Analysis ofHelicobacter pylori cagAPromoter Elements Required for Salt-Induced Upregulation of CagA Expression

2012 ◽  
Vol 80 (9) ◽  
pp. 3094-3106 ◽  
Author(s):  
John T. Loh ◽  
David B. Friedman ◽  
M. Blanca Piazuelo ◽  
Luis E. Bravo ◽  
Keith T. Wilson ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcriptional Start Site ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Content Type ◽  
Dna Motif ◽  
Proteomic Approach ◽  
Increased Risk ◽  
H Pylori

ABSTRACTHelicobacter pyloriinfection and consumption of a high-salt diet are each associated with an increased risk for the development of gastric cancer. To investigate potential synergism between these factors, we used a global proteomic approach to analyzeH. pyloristrains cultured in media containing varying salt concentrations. Among the differentially expressed proteins identified, CagA exhibited the greatest increase in expression in response to high salt concentrations. Analysis of 36H. pyloristrains isolated from patients in two regions of Colombia with differing incidences of gastric cancer revealed marked differences among strains in salt-responsive CagA expression. Sequence analysis of thecagApromoter region in these strains revealed a DNA motif (TAATGA) that was present in either one or two copies. Salt-induced upregulation of CagA expression was detected more commonly in strains containing two copies of the TAATGA motif than in strains containing one copy. Mutagenesis experiments confirmed that two copies of the TAATGA motif are required for salt-induced upregulation of CagA expression. In summary, there is considerable heterogeneity amongH. pyloristrains in salt-regulated CagA expression, and these differences are attributable to variation in a specific DNA motif upstream of thecagAtranscriptional start site.

scholarly journals Helicobacter pylori AdaptationIn Vivoin Response to a High-Salt Diet

2015 ◽  
Vol 83 (12) ◽  
pp. 4871-4883 ◽  
Author(s):  
John T. Loh ◽  
Jennifer A. Gaddy ◽  
Holly M. Scott Algood ◽  
Silvana Gaudieri ◽  
Simon Mallal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Helicobacter Pylori ◽  
High Salt ◽  
Mongolian Gerbils ◽  
High Salt Diet ◽  
Salt Diet ◽  
Content Type ◽  
Regular Diet ◽  
H Pylori ◽  
And Oxidative Stress

Helicobacter pyloriexhibits a high level of intraspecies genetic diversity. In this study, we investigated whether the diversification ofH. pyloriis influenced by the composition of the diet. Specifically, we investigated the effect of a high-salt diet (a known risk factor for gastric adenocarcinoma) onH. pyloridiversification within a host. We analyzedH. pyloristrains isolated from Mongolian gerbils fed either a high-salt diet or a regular diet for 4 months by proteomic and whole-genome sequencing methods. Compared to the input strain and output strains from animals fed a regular diet, the output strains from animals fed a high-salt diet produced higher levels of proteins involved in iron acquisition and oxidative-stress resistance. Several of these changes were attributable to a nonsynonymous mutation infur(fur-R88H). Further experiments indicated that this mutation conferred increased resistance to high-salt conditions and oxidative stress. We propose a model in which a high-salt diet leads to high levels of gastric inflammation and associated oxidative stress inH. pylori-infected animals and that these conditions, along with the high intraluminal concentrations of sodium chloride, lead to selection ofH. pyloristrains that are most fit for growth in this environment.

scholarly journals High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis

2013 ◽  
Vol 81 (6) ◽  
pp. 2258-2267 ◽  
Author(s):  
Jennifer A. Gaddy ◽  
Jana N. Radin ◽  
John T. Loh ◽  
Feng Zhang ◽  
M. Kay Washington ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Salt Intake ◽  
High Salt ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Content Type ◽  
Dietary Salt Intake ◽  
Regular Diet ◽  
H Pylori

ABSTRACTPersistent colonization of the human stomach withHelicobacter pyloriis a risk factor for gastric adenocarcinoma, andH. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT)cagA+H. pyloristrain or an isogeniccagAmutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with thecagAmutant strain (P< 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1β (IL-1β), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with thein vitroresults, we detected increasedcagAtranscriptionin vivoin animals fed a high-salt diet compared to those on a regular diet. Animals infected with thecagAmutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects ofcagA+H. pyloristrains.

Daily intake of sulforaphane-rich broccoli sprouts prevents progression of high salt diet-induced gastric atrophy in H. pylori-infected C57/BL6 mice in vivo

2003 ◽  
Vol 124 (4) ◽  
pp. A5 ◽  
Author(s):  
Akinori Yanaka ◽  
Songhua Zhang ◽  
Masafumi Tauchi ◽  
Hideo Suzuki ◽  
Takeshi Shibahara ◽  
...  
Keyword(s):  
Daily Intake ◽  
Gastric Atrophy ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Broccoli Sprouts ◽  
H Pylori

High nephron endowment protects against salt-induced hypertension

2012 ◽  
Vol 303 (2) ◽  
pp. F253-F258 ◽  
Author(s):  
Kenneth A. Walker ◽  
Xiaochu Cai ◽  
Georgina Caruana ◽  
Merlin C. Thomas ◽  
John F. Bertram ◽  
...  
Keyword(s):  
Renal Function ◽  
Transforming Growth Factor ◽  
Urine Volume ◽  
High Salt ◽  
Nephron Number ◽  
High Salt Diet ◽  
Salt Diet ◽  
Increased Risk ◽  
Functional Consequences ◽  
Transforming Growth Factor Β2

While low nephron number is associated with increased risk of developing cardiovascular and renal disease, the functional consequences of a high nephron number are unknown. We tested the hypothesis that a high nephron number provides protection against hypertensive and renal insults. Mean arterial pressure (MAP) and renal function were characterized in male wild-type (WT) and transforming growth factor-β2 heterozygous ( Tgfb2+/−) mice under basal conditions and following a chronic high-salt diet. Kidneys were collected for unbiased stereological analysis. Baseline MAP and renal function were indistinguishable between genotypes. The chronic high-salt diet (5% NaCl for 4 wk followed by 8% NaCl for 4 wk) led to similar step-wise increases in urine volume, Na+ excretion, and albuminuria in the genotypes. The 5% NaCl diet induced modest and similar increases in MAP (3.5 ± 1.6 and 3.4 ± 0.8 mmHg in WT and Tgfb2+/−, respectively). After the step up to the 8% NaCl diet, MAP increased further in WT (+15.9 ± 5.1 mmHg), but not Tgfb2+/− (−0.1 ± 1.0 mmHg), mice. Nephron number was 30% greater in Tgfb2+/− than WT mice and was not affected by the chronic high-salt diet. Mean glomerular volume was lower in Tgfb2+/− than WT mice, and the chronic high-salt diet induced significant glomerular hypertrophy. In a separate cohort of mice, an acute, 7-day, 8% NaCl diet induced similar rises in MAP in the genotypes. This is the first study to examine the physiological characteristics of a model of high nephron number, and the findings are consistent with this phenotype providing protection against chronic, but not acute, hypertensive insults.

scholarly journals FBPAII and rpoBC, the Two Novel Secreted Proteins Identified by the Proteomic Approach from a Comparative Study between Antibiotic-Sensitive and Antibiotic-Resistant Helicobacter pylori-Associated Gastritis Strains

2021 ◽  
Vol 89 (6) ◽  
Author(s):  
Suthathip Kittisenachai ◽  
Panadda Rojpibulstit ◽  
Ratha-Korn Vilaichone ◽  
Pornpen Gamnarai ◽  
Narumon Phaonakrop ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Secreted Proteins ◽  
Venn Diagram ◽  
Pcr Analysis ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Reverse Transcription Pcr ◽  
Proteomic Approach ◽  
H Pylori

ABSTRACT Helicobacter pylori infection is the leading cause of chronic gastritis, which can develop into gastric cancer. Eliminating H. pylori infection with antibiotics achieves the prevention of gastric cancer. Currently, the prevalence of H. pylori resistance to clarithromycin and metronidazole, and the dual resistance to metronidazole and clarithromycin (C_R, M_R, and C/M_R, respectively), remains at a high level worldwide. As a means of exploring new candidate proteins for the management of H. pylori infection, secreted proteins from antibiotic-susceptible and antibiotic-resistant H. pylori-associated gastritis strains were obtained by in-solution tryptic digestion coupled with nano-liquid chromatography tandem mass spectrometry (nano-LC-MS/MS). A total of 583, 582, 590, and 578 differential expressed proteins were identified from C_R, M_R, C/M_R, and antibiotic-sensitive strain (S_S) samples, respectively. Of these, 23 overlapping proteins were found by Venn diagram analysis. Based on heat map analyses, the most and least differing protein expressions were observed from C/M_R strains and S_S strains, respectively. Of the proteins secreted by the S_S strain, only nine were found. After predicting the protein interaction with metronidazole and clarithromycin via the STITCH database, the two most interesting proteins were found to be rpoBC and FBPAII. After quantitative real-time reverse transcription PCR (qRT-PCR) analysis, a downregulation of rpoB from M_R strains was observed, suggesting a relationship of rpoB to metronidazole sensitivity. Inversely, an upregulation of fba from C_R, M_R, and C/M_R strains was noticed, suggesting the paradoxical expression of FBPAII and the fba gene. This report is the first to demonstrate the association of these two novel secreted proteins, namely, rpoBC and FBPAII, with antibiotic-sensitive H. pylori-associated gastritis strains.

Geranylgeranylacetone prevents progression of high salt diet-induced gastric atrophy in H. pylori-infected C57/BL6 mice via induction of heat shock protein

2003 ◽  
Vol 124 (4) ◽  
pp. A592-A593
Author(s):  
Songhua Zhang ◽  
Akinori Yanaka ◽  
Masafumi Tauchi ◽  
Hideo Suzuki ◽  
Takeshi Shibahara ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Gastric Atrophy ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
H Pylori

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Atrophic Gastritis ◽  
Genetic Polymorphisms ◽  
Association Studies ◽  
Control Group ◽  
Similar Distribution ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Infection Susceptibility ◽  
H Pylori

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.

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