The Helicobacter pylori Urease Virulence Factor Is Required for the Induction of Hypoxia-Induced Factor-1α in Gastric Cells.
Chronic Helicobacter pylori infection increases the risk of gastric cancer and induction of hypoxia-induced factor (HIF), which is frequently associated with the development and progression of several types of cancer. We recently showed that H. pylori activation of the PI3K-AKT-mTOR pathway in gastr...
| Publicado en: | Cancers Vol. 11; no. 6; pp. 799 - 800 |
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| Autores principales: | , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
MDPI
Jun2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=137456433&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 137456433 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Jun2019 vid: 11 iid: 6 pid: 97109 pub: MDPI artinfo: ui: 137456433 137456433 137456433 10.3390/cancers11060799 137456433 ppf: 799 ppct: 1 formats: tig: atl: The Helicobacter pylori Urease Virulence Factor Is Required for the Induction of Hypoxia-Induced Factor-1α in Gastric Cells. aug: au: Valenzuela-Valderrama, Manuel Cerda-Opazo, Paulina Backert, Steffen González, María Fernanda Carrasco-Véliz, Nicolás Jorquera-Cordero, Carla Wehinger, Sergio Canales, Jimena Bravo, Denisse Quest, Andrew F. G. affil: Laboratorio de Microbiología Celular, Instituto de Innovación e Investigación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8320000, Chile sug: subj: Helicobacter Infections Complications Stomach Neoplasms Risk Factors Urease Metabolism Transcription Factors Virulence Animal Studies Rats Mutation Staining and Labeling Methods Polymers Analysis Sodium Electrophoresis Methods Gene Expression Adenocarcinoma Antibodies Toll-Like Receptors Transferases Microbial Culture and Sensitivity Tests ab: Chronic Helicobacter pylori infection increases the risk of gastric cancer and induction of hypoxia-induced factor (HIF), which is frequently associated with the development and progression of several types of cancer. We recently showed that H. pylori activation of the PI3K-AKT-mTOR pathway in gastric cells increased HIF-1α expression. Here, we identified the H. pylori virulence factor responsible for HIF-1α induction. A mutant of the H. pylori 84-183 strain was identified with reduced ability to induce HIF-1α. Coomassie blue staining of extracts from these bacteria separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed poor expression of urease subunits that correlated with reduced urease activity. This finding was confirmed in the 26695 strain, where urease mutants were unable to induce HIF-1α expression. Of note, HIF-1α induction was also observed in the presence of the urease inhibitor acetohydroxamic acid at concentrations (of 20 mM) that abrogated urease activity in bacterial culture supernatants, suggesting that enzymatic activity of the urease is not required for HIF-1α induction. Finally, the pre-incubation of the human gastric adenocarcinoma cell line AGS with blocking antibodies against Toll-like receptor-2 (TLR2), but not TLR4, prevented HIF-1α induction. In summary, these results reveal a hitherto unexpected role for the urease protein in HIF-1α induction via TLR2 activation following H. pylori infection of gastric cells. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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