Role of glutamine and arginase in protection against ammonia-induced cell death in gastric epithelial cells

2002 ◽  
Vol 283 (6) ◽  
pp. G1264-G1275 ◽  
Author(s):  
Eiji Nakamura ◽  
Susan J. Hagen
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Ammonium Chloride ◽  
Gastric Epithelial Cells ◽  
Cytotoxic Factor ◽  
Ammonia Detoxification ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Detoxification Pathways

Ammonia is a cytotoxic factor produced during Helicobacter pylori infection that may reduce the survival of surface epithelial cells. Here we examine whether ammonia kills cells and whether l-glutamine (l-Gln) protects against cell death by stimulating ammonia detoxification pathways. Cell viability and vacuolation were quantified in rat gastric epithelial (RGM1) cells incubated with ammonium chloride at pH 7.4 in the presence or absence of l-Gln. Incubation of RGM1 cells with ammonium chloride caused a dose-dependent increase in cell death and vacuolation, which were both inhibited byl-Gln. We show that RGM1 cells metabolize ammonia to urea via arginase, a process that is stimulated by l-Gln and results in reduced ammonia cytotoxicity. l-Gln also inhibits the uptake and facilitates the extrusion of ammonia from cells. Blockade of glutamine synthetase did not reduce the survival of RGM1 cells, demonstrating that the conversion ofl-glutamate and ammonia to l-Gln is not involved in ammonia detoxification. Thus our data support a role forl-Gln and arginase in protection against ammonia-induced cell death in gastric epithelial cells.

scholarly journals microRNA-29a-3p, Up-Regulated in Human Gastric Cells and Tissues with H.Pylori Infection, Promotes the Migration of GES-1 Cells via A20-Mediated EMT Pathway

2018 ◽  
Vol 51 (3) ◽  
pp. 1250-1263 ◽  
Author(s):  
Fengying Sun ◽  
Ying Ni ◽  
Hong Zhu ◽  
Jian Fang ◽  
Hua Wang ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Human Gastric Mucosa ◽  
Gastric Epithelial Cells ◽  
Migration Ability ◽  
Gastric Cells ◽  
Dose Dependent

Background/Aims: Helicobacter pylori (H. pylori) infection is closely related to human gastric mucosa-associated diseases. Several recent studies on miRNAs have expanded our insights on H.pylori pathogenesis. This study aimed to investigate the biological roles and underlying molecular mechanisms of miR-29a-3p in human gastric cells and tissues with H.pylori infection. Methods: miR-29a-3p expression was quantified by quantitative RT-PCR (qRT-PCR). A miR-29a-3p target gene was validated by bioinformatics analysis, western blotting and dual luciferase reporter gene assays. Western blotting and immunohistochemistry (IHC) assay were performed to detect the protein expression. Transwell assay was used to determine the cell migration ability. Results: MiR-29a-3p was up-regulated in H.pylori-positive gastric mucosa tissues and H.pylori-infected gastric cells. The up-regulation of miR-29a-3p was dose-dependent in BGC-823 and GES-1 cells infected with H.pylori. Using gain- and loss-of-function experiments in vitro, we demonstrated that miR-29a-3p promoted the migration of gastric epithelial cells. We further characterized A20 as a direct target of miR-29a-3p. The expression of A20 was decreased in H.pylori-positive gastric mucosa tissues compared with H.pylori-negative gastric mucosa tissues. A20 downregulation was time- and dose-dependent in GES-1 and BGC-823 cells infected with H.pylori. In GES-1 and BGC-823 cells infected with H.pylori, the miR-29a-3p mimic significantly blocked A20 expression, which suggests that H.pylori decreased A20 expression through up-regulating miR-29a-3p in GES-1 and BGC-823 cells infected with H.pylori. The knockdown of A20 by siRNA enhanced the migration of human gastric epithelial cells and promoted the expression of Snail, Vimentin, and N-cadherin and inhibited the expression of E-cadherin. Conclusion: The miR-29a-3p may act as a tumor promotive miRNA by regulating cells migration through directly targeting of A20 gene in human gastric epithelial cells infected with H.pylori.

1092 Interferon-γ Acts Directly on Gastric Epithelial Cells by Regulating Cell Death

2016 ◽  
Vol 150 (4) ◽  
pp. S218
Author(s):  
Luciana H. Osaki ◽  
Kevin Bockerstett ◽  
Eric Ford ◽  
Richard DiPaolo ◽  
Jason Mills
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Interferon Γ ◽  
Gastric Epithelial Cells

scholarly journals Helicobacter pylori Induces Gastric Epithelial Cell Apoptosis in Association with Increased Fas Receptor Expression

1999 ◽  
Vol 67 (8) ◽  
pp. 4237-4242 ◽  
Author(s):  
Nicola L. Jones ◽  
Andrew S. Day ◽  
Hilary A. Jennings ◽  
Philip M. Sherman
Keyword(s):  
Cell Death ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Receptor Expression ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
Fas Receptor ◽  
Epithelial Cell Apoptosis ◽  
H Pylori

ABSTRACT The mechanisms involved in mediating the enhanced gastric epithelial cell apoptosis observed during infection withHelicobacter pylori in vivo are unknown. To determine whether H. pylori directly induces apoptosis of gastric epithelial cells in vitro and to define the role of the Fas-Fas ligand signal transduction cascade, human gastric epithelial cells were infected with H. pylori for up to 72 h under microaerophilic conditions. As assessed by both transmission electron microscopy and fluorescence microscopy, incubation with acagA-positive, cagE-positive, VacA-positive clinical H. pylori isolate stimulated an increase in apoptosis compared to the apoptosis of untreated AGS cells (16.0% ± 2.8% versus 5.9% ± 1.4%, P < 0.05) after 72 h. In contrast, apoptosis was not detected following infection withcagA-negative, cagE-negative, VacA-negative clinical isolates or a Campylobacter jejuni strain. In addition to stimulating apoptosis, infection with H. pylorienhanced Fas receptor expression in AGS cells to a degree comparable to that of treatment with a positive control, gamma interferon (12.5 ng/ml) (148% ± 24% and 167% ± 24% of control, respectively). The enhanced Fas receptor expression was associated with increased sensitivity to Fas-mediated cell death. Ligation of the Fas receptor with an agonistic monoclonal antibody resulted in an increase in apoptosis compared to the apoptosis of cells infected with the bacterium alone (38.5% ± 7.1% versus 16.0% ± 2.8%,P < 0.05). Incubation with neutralizing anti-Fas antibody did not prevent apoptosis of H. pylori-infected cells. Taken together, these findings demonstrate that the gastric pathogen H. pylori stimulates apoptosis of gastric epithelial cells in vitro in association with the enhanced expression of the Fas receptor. These data indicate a role for Fas-mediated signaling in the programmed cell death that occurs in response toH. pylori infection.

scholarly journals Hyperinsulinemia, But Not Other Factors Associated with Insulin Resistance, Acutely Enhances Colorectal Epithelial Proliferation in Vivo

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1830-1837 ◽  
Author(s):  
Thien T. Tran ◽  
Dinaz Naigamwalla ◽  
Andrei I. Oprescu ◽  
Loretta Lam ◽  
Gail McKeown-Eyssen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Epithelial Cells ◽  
Dependent Manner ◽  
Epithelial Proliferation ◽  
Euglycemic Clamp ◽  
The Individual ◽  
Dose Dependent ◽  
Circulating Levels

The similarity in risk factors for insulin resistance and colorectal cancer (CRC) led to the hypothesis that markers of insulin resistance, such as elevated circulating levels of insulin, glucose, fatty acids, and triglycerides, are energy sources and growth factors in the development of CRC. The objective was thus to examine the individual and combined effects of these circulating factors on colorectal epithelial proliferation in vivo. Rats were fasted overnight, randomized to six groups, infused iv with insulin, glucose, and/or Intralipid for 10 h, and assessed for 5-bromo-2-deoxyuridine labeling of replicating DNA in colorectal epithelial cells. Intravenous infusion of insulin, during a 10-h euglycemic clamp, increased colorectal epithelial proliferation in a dose-dependent manner. The addition of hyperglycemia to hyperinsulinemia did not further increase proliferation. Intralipid infusion alone did not affect proliferation; however, the combination of insulin, glucose, and Intralipid infusion resulted in greater hyperinsulinemia than the infusion of insulin alone and further increased proliferation. Insulin infusion during a 10-h euglycemic clamp decreased total IGF-I levels and did not affect insulin sensitivity. These results provide evidence for an acute role of insulin, at levels observed in insulin resistance, in the proliferation of colorectal epithelial cells in vivo.

scholarly journals Helicobacter pylori–induced matrix metallopeptidase-10 promotes gastric bacterial colonization and gastritis

2019 ◽  
Vol 5 (4) ◽  
pp. eaau6547 ◽  
Author(s):  
Yi-pin Lv ◽  
Ping Cheng ◽  
Jin-yu Zhang ◽  
Fang-yuan Mao ◽  
Yong-sheng Teng ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bacterial Colonization ◽  
Gastric Epithelium ◽  
Erk Pathway ◽  
Gastric Epithelial Cells ◽  
Zonula Occludens ◽  
Matrix Metallopeptidase ◽  
Zonula Occludens 1 ◽  
H Pylori

The interaction between gastric epithelium and immune response plays key roles in H. pylori–associated pathology. We demonstrated a procolonization and proinflammation role of MMP-10 in H. pylori infection. MMP-10 is elevated in gastric mucosa and is produced by gastric epithelial cells synergistically induced by H. pylori and IL-22 via the ERK pathway. Human gastric MMP-10 was correlated with H. pylori colonization and the severity of gastritis, and mouse MMP-10 from non–BM-derived cells promoted bacteria colonization and inflammation. H. pylori colonization and inflammation were attenuated in IL-22−/−, MMP-10−/−, and IL-22−/−MMP-10−/− mice. MMP-10–associated inflammation is characterized by the influx of CD8+ T cells, whose migration is induced via MMP-10–CXCL16 axis by gastric epithelial cells. Under the influence of MMP-10, Reg3a, E-cadherin, and zonula occludens–1 proteins decrease, resulting in impaired host defense and increased H. pylori colonization. Our results suggest that MMP-10 facilitates H. pylori persistence and promotes gastritis.

Chemopreventive Agent Resveratrol, a Natural Product Derived From Grapes, Triggers CD95 Signaling-Dependent Apoptosis in Human Tumor Cells

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 996-1002 ◽  
Author(s):  
Marie-Véronique Clément ◽  
Jayshreekumari L. Hirpara ◽  
Sanaul-Haq Chawdhury ◽  
Shazib Pervaiz
Keyword(s):  
Cell Death ◽  
Natural Product ◽  
Tumor Cells ◽  
Leukemia Cell ◽  
Human Tumor ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
Resveratrol Treatment ◽  
Dose Dependent Increase ◽  
Dose Dependent

Resveratrol, a constituent of grapes and other food products, has been shown to prevent carcinogenesis in murine models. We report here that resveratrol induces apoptotic cell death in HL60 human leukemia cell line. Resveratrol-treated tumor cells exhibit a dose-dependent increase in externalization of inner membrane phosphatidylserine and in cellular content of subdiploid DNA, indicating loss of membrane phospholipid asymmetry and DNA fragmentation. Resveratrol-induced cell death is mediated by intracellular caspases as observed by the dose-dependent increase in proteolytic cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and the ability of caspase inhibitors to block resveratrol cytotoxicity. We also show that resveratrol treatment enhances CD95L expression on HL60 cells, as well as T47D breast carcinoma cells, and that resveratrol-mediated cell death is specifically CD95-signaling dependent. On the contrary, resveratrol treatment of normal human peripheral blood lymphocytes (PBLs) does not affect cell survival for up to 72 hours, which correlates with the absence of a significant change in either CD95 or CD95L expression on treated PBLs. These data show specific involvement of the CD95-CD95L system in the anti-cancer activity of resveratrol and highlight the chemotherapeutic potential of this natural product, in addition to its recently reported chemopreventive activity. © 1998 by The American Society of Hematology.

Identification, regulation and anti-proliferative role of the NPR-C receptor in gastric epithelial cells

2006 ◽  
Vol 293 (1-2) ◽  
pp. 103-118 ◽  
Author(s):  
William R. Gower ◽  
Gay M. Carter ◽  
Quentin McAfee ◽  
Suzanne M. Solivan
Keyword(s):  
Epithelial Cells ◽  
Gastric Epithelial Cells
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