A Novel Effect of Bismuth Ions

Pannequin, Julie; Kovac, Suzana; Tantiongco, John-Paul; Norton, Raymond S.; Shulkes, Arthur; Barnham, Kevin J.; Baldwin, Graham S.

doi:10.1074/jbc.m309806200

Cited by 28 publications

(23 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next we treated Jurkat cells with sequential doses of TFF2 (600 nM) and SDF-1␣ (12.5 nM) and vice versa. In this experiment we also introduced a third (control) treatment of amidated gastrin (Gas 17 ) because the CCK-2 G-protein-coupled receptor is expressed on Jurkat cells (40). Pretreatment of Jurkat cells with TFF2 decreased the Ca 2ϩ flux induced by SDF-1␣ by 40 -60% (Fig.…”

Section: Cxcr4 Receptor Is Necessary For Tff2-stimulated Ca 2ϩ Flux Imentioning

confidence: 99%

Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines

Dubeykovskaya

Dubeykovskiy

Solal-Cohen

et al. 2009

Journal of Biological Chemistry

106

View full text Add to dashboard Cite

The secreted trefoil factor family 2 (TFF2) protein contributes to the protection of the gastrointestinal mucosa from injury by strengthening and stabilizing mucin gels, stimulating epithelial restitution, and restraining the associated inflammation. Although trefoil factors have been shown to activate signaling pathways, no cell surface receptor has been directly linked to trefoil peptide signaling. Here we demonstrate the ability of TFF2 peptide to activate signaling via the CXCR4 chemokine receptor in cancer cell lines. We found that both mouse and human TFF2 proteins (at ϳ0.5 M) activate Ca 2؉ signaling in lymphoblastic Jurkat cells that could be abrogated by receptor desensitization (with SDF-1␣) or pretreatment with the specific antagonist AMD3100 or an anti-CXCR4 antibody. TFF2 pretreatment of Jurkat cells decreased Ca 2؉ rise and chemotactic response to SDF-1␣. In addition, the CXCR4-negative gastric epithelial cell line AGS became highly responsive to TFF2 treatment upon expression of the CXCR4 receptor. TFF2-induced activation of mitogen-activated protein kinases in gastric and pancreatic cancer cells, KATO III and AsPC-1, respectively, was also dependent on the presence of the CXCR4 receptor. Finally we demonstrate a distinct proliferative effect of TFF2 protein on an AGS gastric cancer cell line that expresses CXCR4. Overall these data identify CXCR4 as a bona fide signaling receptor for TFF2 and suggest a mechanism through which TFF2 may modulate immune and tumorigenic responses in vivo.

show abstract

Section: Cxcr4 Receptor Is Necessary For Tff2-stimulated Ca 2ϩ Flux Imentioning

confidence: 99%

Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines

Dubeykovskaya

Dubeykovskiy

Solal-Cohen

et al. 2009

Journal of Biological Chemistry

106

View full text Add to dashboard Cite

show abstract

“…Iron binding was 53 critical for Ggly bioactivity in vitro (27) and in vivo (13, 22), but was not necessary for Gamide to 54 activate the CCK2 receptor (29). Bismuth ions can block Ggly activity by displacing iron (22,28). 55…”

mentioning

confidence: 99%

Increased gastrin gene expression provides a physiological advantage to mice under hypoxic conditions

Laval

Baldwin

Shulkes

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

View full text Add to dashboard Cite

Hypoxia, or a low concentration of O2, is encountered in humans undertaking activities such as mountain climbing and scuba diving and is important pathophysiologically as a limiting factor in tumor growth. Although data on the interplay between hypoxia and gastrins are limited, gastrin expression is upregulated by hypoxia in gastrointestinal cancer cell lines, and gastrins counterbalance hypoxia by stimulating angiogenesis in vitro and in vivo. The aim of this study was to determine if higher concentrations of the gastrin precursor progastrin are protective against hypoxia in vivo. hGAS mice, which overexpress progastrin in the liver, and mice of the corresponding wild-type FVB/N strain were exposed to normoxia or hypoxia. Iron status was assessed by measurement of serum iron parameters, real-time PCR for mRNAs encoding critical iron regulatory proteins, and Perls' stain and atomic absorption spectrometry for tissue iron concentrations. FVB/N mice lost weight at a faster rate and had higher sickness scores than hGAS mice exposed to hypoxia. Serum iron levels were lower in hGAS than FVB/N mice and decreased further when the animals were exposed to hypoxia. The concentration of iron in the liver was strikingly lower in hGAS than FVB/N mice. We conclude that increased circulating concentrations of progastrin provide a physiological advantage against systemic hypoxia in mice, possibly by increasing the availability of iron stores. This is the first report of an association between progastrin overexpression, hypoxia, and iron homeostasis.

show abstract

“…Bismuth was found to be an inhibitor against the biological activity of glycine extended gastrin 17 (Ggly) in stimulating inositol phosphate production, cell proliferation and cell migration [53]. Fluorescence experiments show that both Ggly and amidated gastrin 17 (Gamide) (Figure 3.9) bind two Fe III or Bi III ions [54,55].…”

Section: Interaction Of Bismuth With Amino Acids and Peptidesmentioning

confidence: 99%