Inhibition of cell proliferation and induction of apoptosis by Helicobacter pylori through increased phosphorylated p53, p21 and Bax expression in endothelial cells

Kurosawa, Akihiko; Miwa, Hiroto; Hirose, Miyoko; Tsune, Isao; Nagahara, Akihito; Sato, Nobuhiro

doi:10.1099/0022-1317-51-5-385

Cited by 24 publications

(27 citation statements)

References 36 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study also supports the anti-angiogenic effects of H. pylori on ECs shown in recent studies [22, 39, 48, 51](summarized in table 1). …”

Section: Discussionsupporting

confidence: 77%

“…Studies based on both human biopsy specimens and in vivo models have demonstrated an association between H. pylori infection and increased proliferation of gastric mucosal epithelial cells [22, 23, 24, 25, 26]for a review see 27]. In contrast, H. pylori produces an antiproliferative effect on epithelial cells, macrophages, and lymphocytes [28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of <i>Helicobacter pylori </i>on Endothelial Cell Proliferation and Chemotaxis

Pearce¹,

Kalia²,

Bardhan³

et al. 2004

Digestion

View full text Add to dashboard Cite

Background/Aim:Helicobacter pylori is associated with an increased risk of peptic ulcer disease development and recurrence. Ulcer healing is dependent upon angiogenesis, requiring endothelial cell (EC) proliferation and chemotaxis. This study determined whether extracts of H. pylori affected EC proliferation and/or chemotaxis in vitro. Methods: The effects of water and broth extracts of three genotypically different strains of H. pylori and of single strains of Campylobacter jejuni and Escherichia coli on human dermal microvascular EC (HuDMEC) and human umbilical vein EC (HUVEC) were assessed. Tetrazolium dye (MTT) proliferation, dual staining cell viability, flow cytometry, and microchemotaxis assays were performed. Results:H. pylori (all strains) and C. jejuni inhibited HuDMEC (p < 0.01) and HUVEC (p < 0.01) proliferation and decreased the proportion of HUVECs in the S phase of the cell cycle. E. coli had no effect on EC proliferation. The levels of vascular endothelial growth factor stimulated chemotaxis were significantly greater (p < 0.01) than the levels of basal migration for both control and extract-treated ECs. However, none of the bacterial extracts affected EC basal migration or chemotaxis. Conclusion:H. pylori extracts inhibit HuDMEC and HUVEC proliferation in vitro by a cytostatic, strain-independent mechanism. A similar antiproliferative effect of C. jejuni was observed. Our findings suggest that both H. pylori and C. jejuni have the ability to inhibit one of the key stages of angiogenesis which may have implications in peptic ulcer disease.

show abstract

“…The present study also supports the anti-angiogenic effects of H. pylori on ECs shown in recent studies [22, 39, 48, 51](summarized in table 1). …”

Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Effects of <i>Helicobacter pylori </i>on Endothelial Cell Proliferation and Chemotaxis

Pearce¹,

Kalia²,

Bardhan³

et al. 2004

Digestion

View full text Add to dashboard Cite

show abstract

“…Although previous data indicated its importance in H. pylori infection [17, 18], aberrant DNA methylation of the p21 gene may be very rare in the stomach.…”

Section: Discussionmentioning

confidence: 95%

“…Methylation of p16 and p14 has been shown to be present in gastric cancer as well as premalignant lesions [14, 15]. p21(Waf1) is also involved in cell cycle arrest [16], which is upregulated in H. pylori infection [17, 18]. These genes may play crucial roles in cell cycle control, apoptosis and DNA repair in the stomach and its disorder may be closely associated with gastric carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Risk Prediction of Gastric Cancer by Analysis of Aberrant DNA Methylation in Non-Neoplastic Gastric Epithelium

et al. 2007

View full text Add to dashboard Cite

Background: Aberrant DNA methylation is one of the major events in carcinogenesis. Promoter DNA methylation is also present in various non-neoplastic tissues including gastric epithelium as age-related phenomenon, suggesting that it occurs early in the process of tumorigenesis. Aim: We aimed to clarify the relationship of aberrant DNA methylation in non-neoplastic gastric epithelia with the risk of gastric cancer, Helicobactor pylori infection, and the degree of H. pylori-induced gastritis. Methods: 89 patients enrolled in this study. The status of aberrant DNA methylation was compared in two groups of patients: 43 cases with gastric cancer (mean age 65.9 years [29–91], F:M = 0.30, intestinal type [n = 25], diffuse type [n = 18]) and 46 age- and sex-matched patients without gastric cancer (peptic ulcer diseases [n = 11], gastritis [n = 35]) as a control group. Genomic DNA was extracted directly from non-neoplastic epithelia of antral biopsies obtained by endoscopy. The promoter methylation status of the p14 and p21 genes was determined by methylation-specific-polymerase chain reaction (MSP). The promoter methylation status of the p16 gene was quantified by digital densitographic analysis following MSP. The degree of gastritis in the antrum was assessed according to the updated Sydney system. The PG I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay. Results: In all 89 subjects, CpG island methylation was found in 25.8% for p14, 52.8% for p16, 1.1% for p21. Among non-cancer patients, the methylation frequency of the p14 gene was significantly higher in H. pylori-positive than in H. pylori-negative patients (38.5 vs. 10.0%, p = 0.03). The mean (± SD) methylation levels of the p16 gene in non-neoplastic gastric epithelium was significantly higher in gastric cancer cases both in all patients and in H. pylori-positive patients (0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.019, 0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.016, respectively). The methylation level of the p16 gene was also associated with the presence of intestinal-type gastric cancer (p = 0.017). The methylation level of the p16 gene was significantly higher in patients with intestinal metaplasia (IM) than those without (p = 0.04). Furthermore, the methylation level of the p16 gene was correlated with lower PG l/ll ratio (p = 0.04). The methylation of the p21gene was found in only 1 patient with gastric cancer. Conclusions: Our data suggest that promoter of the p14 gene may be one of the specific regions whose methylation is closely associated with H. pylori infection. Methylation levels of the p16 gene seem to be accumulated in the progression of gastric mucosal atrophy and IM, and thus may be associated with the presence of gastric cancer especially for intestinal-type histopathology.

show abstract

“…The RT step was carried out at 42°C for 30 min followed by denaturation for 5 min at 95°C. PCR was performed as follows: 1 min at 95°C, 1 min with primers and at annealing temperature as outline in table 1[22,23,24,25,26], followed by extension for 1 min at 72°C. RT-PCR products were visualised on a 2% (w/v) agarose gel, stained with SYBR Green I (FMC BioProducts, Rockland, Me., USA).…”

Section: Methodsmentioning

confidence: 99%

The Influence of Exogenous Tissue Factor on the Regulators of Proliferation and Apoptosis in Endothelial Cells

Pradier

Ettelaie²

2007

J Vasc Res

View full text Add to dashboard Cite

Background: The exposure of tissue factor (TF) at the site of injury or trauma is a rapid process that leads to the initiation of blood coagulation as well as homeostatic processes giving rise to vascular repair. Aims and Methods: By exposing human endothelial cells to combinations of exogenous TF and factor VIIa (FVIIa) in serum-free medium, the influence of TF concentrations on cellular proliferation and apoptosis was investigated. Results: Lower concentrations of TF resulted in increased cellular proliferation as well as upregulation of cyclin D1, downregulation of p21 and p27 and induction of tube formation in vitro. Conversely, incubation with higher concentrations of TF resulted in the activation of caspase-3, expression of p53 and Bax, translocation of p53 into the nucleus and induction of DNA fragmentation. Incubation of the cells with TF/FVIIa led to a lower proliferation rate with additional upregulation in p27. Conclusions: TF seems to have a bifunctional role in determining the fate of endothelial cells, depending on the concentration and the interactions of this protein. The release of TF in the locality of the injured tissue makes this protein an ideal factor for ascertaining the level of injury and determining the fate of the cells.

show abstract

Inhibition of cell proliferation and induction of apoptosis by Helicobacter pylori through increased phosphorylated p53, p21 and Bax expression in endothelial cells

Cited by 24 publications

References 36 publications

Effects of <i>Helicobacter pylori </i>on Endothelial Cell Proliferation and Chemotaxis

Effects of <i>Helicobacter pylori </i>on Endothelial Cell Proliferation and Chemotaxis

Risk Prediction of Gastric Cancer by Analysis of Aberrant DNA Methylation in Non-Neoplastic Gastric Epithelium

The Influence of Exogenous Tissue Factor on the Regulators of Proliferation and Apoptosis in Endothelial Cells

Contact Info

Product

Resources

About