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

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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
Externally publishedYes

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DNA-(Apurinic or Apyrimidinic Site) Lyase
Endonucleases
Acetylation
Helicobacter pylori
Stomach
Pylorus
Epithelial Cells
Apoptosis
Cytochromes c
Infection
Histone Deacetylase 1
Poly Adenosine Diphosphate Ribose
Calcium
Chromatin Immunoprecipitation
Response Elements
DNA Fragmentation
Luciferases
Fluorescence Microscopy
Immunoprecipitation
Immunoblotting

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Bhattacharyya, A., Chattopadhyay, R., Burnette, B. R., Cross, J. V., Mitra, S., Ernst, P. B., ... Crowe, S. E. (2009). Acetylation of Apurinic/Apyrimidinic Endonuclease-1 Regulates Helicobacter pylori-Mediated Gastric Epithelial Cell Apoptosis. Gastroenterology, 136(7), 2258-2269. https://doi.org/10.1053/j.gastro.2009.02.014

Acetylation of Apurinic/Apyrimidinic Endonuclease-1 Regulates Helicobacter pylori-Mediated Gastric Epithelial Cell Apoptosis. / Bhattacharyya, Asima; Chattopadhyay, Ranajoy; Burnette, Brent R.; Cross, Janet V.; Mitra, Sankar; Ernst, Peter B.; Bhakat, Kishor K.; Crowe, Sheila E.

In: Gastroenterology, Vol. 136, No. 7, 06.2009, p. 2258-2269.

Research output: Contribution to journalArticle

Bhattacharyya, A, Chattopadhyay, R, Burnette, BR, Cross, JV, Mitra, S, Ernst, PB, Bhakat, KK & Crowe, SE 2009, 'Acetylation of Apurinic/Apyrimidinic Endonuclease-1 Regulates Helicobacter pylori-Mediated Gastric Epithelial Cell Apoptosis', Gastroenterology, vol. 136, no. 7, pp. 2258-2269. https://doi.org/10.1053/j.gastro.2009.02.014
Bhattacharyya, Asima ; Chattopadhyay, Ranajoy ; Burnette, Brent R. ; Cross, Janet V. ; Mitra, Sankar ; Ernst, Peter B. ; Bhakat, Kishor K. ; Crowe, Sheila E. / Acetylation of Apurinic/Apyrimidinic Endonuclease-1 Regulates Helicobacter pylori-Mediated Gastric Epithelial Cell Apoptosis. In: Gastroenterology. 2009 ; Vol. 136, No. 7. pp. 2258-2269.
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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.",
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AU - Bhattacharyya, Asima

AU - Chattopadhyay, Ranajoy

AU - Burnette, Brent R.

AU - Cross, Janet V.

AU - Mitra, Sankar

AU - Ernst, Peter B.

AU - Bhakat, Kishor K.

AU - Crowe, Sheila E.

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AB - 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.

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