In vivo accumulation of Helicobacter pylori products, NOD1, ubiquitinated proteins and proteasome in a novel cytoplasmic structure

Vittorio Necchi, Patrizia Sommi, Vittorio Ricci, Enrico Solcia

Research output: Contribution to journalArticle

Abstract

Cell internalization and intracellular fate of H. pylori products/virulence factors in vivo by human gastric epithelium, the main target of H. pylori-induced pathologies (i.e., peptic ulcer and cancer), are still largely unknown. Investigating gastric endoscopic biopsies from dyspeptic patients by means of ultrastructural immunocytochemistry, here we show that, in human superficial-foveolar epithelium and its metaplastic or dysplastic foci, H. pylori virulence factors accumulated in a discrete cytoplasmic structure characterized by 13-nm-thick cylindrical particles of regular punctate-linear substructure resembling the proteasome complex in size and structure. Inside this particle-rich cytoplasmic structure (PaCS) we observed colocalization of VacA, CagA, urease and outer membrane proteins with NOD1 receptor, ubiquitin-activating enzyme E1, polyubiquitinated proteins, proteasome components and potentially oncogenic proteins like SHP2 and ERKs in human gastric epithelium. By means of electron and confocal microscopy, we demonstrate that the in vivo findings were reproduced in vitro by incubating human epithelial cell lines with H. pylori products/virulence factors. PaCSs differed from VacA-induced vacuoles, phagosomes, aggresomes or related bodies. Our data suggest that PaCS is a novel, proteasomeenriched structure arising in ribosome-rich cytoplasm at sites of H. pylori products accumulation. As a site of selective concentration of bacterial virulence factors, the ubiquitin-proteasome system and interactive proteins, PaCS is likely to modulate immune-inflammatory and proliferative responses of the gastric epithelium of potential pathologic relevance.

Original languageEnglish
Article numbere9716
JournalPLoS One
Volume5
Issue number3
DOIs
Publication statusPublished - 2010

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Ubiquitinated Proteins
Cytoplasmic Structures
Helicobacter pylori
proteasome endopeptidase complex
Virulence Factors
Proteasome Endopeptidase Complex
Stomach
stomach
virulence
epithelium
Epithelium
Ubiquitin-Activating Enzymes
proteins
Proteins
Urease
Biopsy
Confocal microscopy
peptic ulcers
Pathology
phagosomes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

In vivo accumulation of Helicobacter pylori products, NOD1, ubiquitinated proteins and proteasome in a novel cytoplasmic structure. / Necchi, Vittorio; Sommi, Patrizia; Ricci, Vittorio; Solcia, Enrico.

In: PLoS One, Vol. 5, No. 3, e9716, 2010.

Research output: Contribution to journalArticle

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