Acetylation of Apurinic/Apyrimidinic Endonuclease-1 Regulates Helicobacter pylori-Mediated Gastric Epithelial Cell Apoptosis

Asima Bhattacharyya, Ranajoy Chattopadhyay, Brent R. Burnette, Janet V. Cross, Sankar Mitra, Peter B. Ernst, Kishor K. Bhakat, Sheila E. Crowe

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Background & Aims: Helicobacter pylori-induced gastric epithelial cell (GEC) apoptosis is a complex process that includes activation of the tumor suppressor p53. p53-mediated apoptosis involves p53 activation, bax transcription, and cytochrome c release from mitochondria. Apurinic/apyrimidinic endonuclease-1 (APE-1) regulates transcriptional activity of p53, and H pylori induce APE-1 expression in human GECs. H pylori infection increases intracellular calcium ion concentration [Ca2+]i of GECs, which induces APE-1 acetylation. We investigated the effects of H pylori infection and APE-1 acetylation on GEC apoptosis. Methods: AGS cells (wild-type or with suppressed APE-1), KATO III cells, and cells isolated from gastric biopsy specimens were infected with H pylori. Effects were examined by immunoblotting, real-time reverse-transcription polymerase chain reaction, immunoprecipitation, immunofluorescence microscopy, chromatin immunoprecipitation, mobility shift, DNA binding, and luciferase assays. Results: H pylori infection increased [Ca2+]i and acetylation of APE-1 in GECs, but the acetylation status of APE-1 did not affect the transcriptional activity of p53. In GECs, expression of a form of APE-1 that could not be acetylated increased total and mitochondrial levels of Bax and induced release of cytochrome c and fragmentation of DNA; expression of wild-type APE-1 reduced these apoptotic events. We identified a negative calcium response element in the human bax promoter and found that poly (adenosine diphosphate-ribose) polymerase 1 recruited the acetylated APE-1/histone deacetylase-1 repressor complex to bax nCaRE. Conclusions: H pylori-mediated acetylation of APE-1 suppresses Bax expression; this prevents p53-mediated apoptosis when H pylori infect GECs.

Original languageEnglish (US)
Pages (from-to)2258-2269
Number of pages12
JournalGastroenterology
Volume136
Issue number7
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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