Effect of<i>Helicobacter pylori</i>’s vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells

Terebiznik, Mauricio R.; Raju, Deepa; Vázquez, Cristina Lourdes; Torbricki, Karl; Kulkarni, Reshma; Blanke, Steven R.; Yoshimori, Tamotsu; Colombo, María Isabel; Jones, Nicola L.

doi:10.4161/auto.5.3.7663

Cited by 195 publications

(244 citation statements)

References 45 publications

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“…1 A recent study from our lab shows the ability of H. pylori and specifically the VacA toxin to induce autophagy in host cells, a process by which VacA toxin is degraded within the host cells. 24 Thus, this is an excellent model system for further defining the mechanism of induction of autophagy and its consequences on the survival of H. pylori. Future studies evaluating these mechanisms will provide insights into host responses against H. pylori infection and specifically the role of autophagy during infection.…”

Section: Discussionmentioning

confidence: 99%

“…In summary, these studies show that VacA-induced autophagy plays a role in degradation of the toxin, thus limiting toxin-induced host cell damage. 24 …”

Section: Preparation Of Concentrated Culture Supernatantsmentioning

confidence: 99%

“…Inhibition of autophagy in Atg12-siRNA treated cells is confirmed by lack of GFP-LC3 aggregation and conversion of LC3-I to LC3-II. 24 …”

Section: Counting and Analysis Of Autophagosomesmentioning

confidence: 99%

“…2). 24 The protocols for both these processes with respect to H. pylori are described below. (4) After 6 h, cells are washed with PBS and fixed with 4% paraformaldehyde (diluted 1 in 4 from a 16% solution) (EMS Inc., 15710).…”

Section: Advantages Of Utilizing H Pylorimentioning

confidence: 99%

“…The autophagosome then fuses with lysosomes Toronto, ON Canada conversion of LC3-I to LC3-II by immunoblot and GFP-LC3 puncta formation as observed by confocal microscopy. 24 Transmission electron microscopy shows the presence of early and late stage autophagosomes with bacteria entrapped within the autophagosomes in response to H. pylori infection (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

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Methods to monitor autophagy inH. pylorivacuolating cytotoxin A (VacA)-treated cells

Raju

Jones²

2010

Autophagy

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Section: Discussionmentioning

confidence: 99%

“…In summary, these studies show that VacA-induced autophagy plays a role in degradation of the toxin, thus limiting toxin-induced host cell damage. 24 …”

Section: Preparation Of Concentrated Culture Supernatantsmentioning

confidence: 99%

“…Inhibition of autophagy in Atg12-siRNA treated cells is confirmed by lack of GFP-LC3 aggregation and conversion of LC3-I to LC3-II. 24 …”

Section: Counting and Analysis Of Autophagosomesmentioning

confidence: 99%

Section: Advantages Of Utilizing H Pylorimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Methods to monitor autophagy inH. pylorivacuolating cytotoxin A (VacA)-treated cells

Raju

Jones²

2010

Autophagy

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Helicobacter PyloriInfection Control by Autophagy

Greenfield

Dang

Jones

2014

Autophagy, Infection, and the Immune Response

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Autophagy impairment byHelicobacter pylori-induced methylation silencing ofMAP1LC3Av1promotes gastric carcinogenesis

et al. 2017

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Helicobacter pylori (H. pylori) infection induces methylation silencing of tumor suppressor genes causing gastric carcinogenesis. Impairment of autophagy induces DNA damage leading to genetic instability and carcinogenesis. We aimed to identify whether H. pylori infection induced methylation silencing of host autophagy-related (Atg) genes, impairing autophagy and enhancing gastric carcinogenesis. Gastric mucosae were obtained from 41 gastric cancer patients and 11 healthy volunteers (8 H. pylori-uninfected and 3 H. pylori-infected). Methylation status of Atg genes was analyzed by a methylation microarray and quantitative methylation-specific PCR (qMSP); mRNA expression was assessed by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation, migration and invasion were assessed in normal rat gastric epithelial cells. Gene knock-down was performed by siRNA. Autophagy was assessed by western blotting. Of 34 Atg genes, MAP1LC3A variant 1 (MAP1LC3Av1) and ULK2 were identified by methylation microarray analysis as exhibiting specific methylation in H. pylori-infected mucosae and gastric cancer tissues. Methylation silencing of MAP1LC3Av1 was confirmed by qMSP, qRT-PCR and de-methylation treatment in two gastric cancer cell lines. Knock-down of map1lc3a, the rat homolog of the human MAP1LC3Av1, inhibited autophagy response and increased cell proliferation, migration and invasion in normal rat gastric epithelial cells, despite the presence of map1lc3b, the rat homolog of the human MAP1LC3B gene important for autophagy. Furthermore, MAP1LC3Av1 was methylation-silenced in 23.3% of gastric cancerous mucosae and 40% of non-cancerous mucosae with H. pylori infection. MAP1LC3Av1 is essential for autophagy and H. pylori-induced methylation silencing of MAP1LC3Av1 may impair autophagy, facilitating gastric carcinogenesis.Gastric cancer is one of the most common cancers worldwide and is among the top three leading causes of cancer-related deaths.1,2 Compelling evidence links Helicobacter pylori (H. pylori) infection to the initiation of a sequence of events that lead from chronic active gastritis to atrophic gastritis, intestinal metaplasia, dysplasia and finally gastric adenocarcinoma. [3][4][5] Several factors, such as nitric oxide, signal transducer and activator of transcription 3 and nuclear factor-jB, have been reported to be responsible for the development of H. pylori-associated gastric cancer 6,7 ; however, the exact

show abstract

Effect ofHelicobacter pylori’s vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells

Abstract: Host cell responses to

Cited by 195 publications

References 45 publications

Methods to monitor autophagy inH. pylorivacuolating cytotoxin A (VacA)-treated cells

Methods to monitor autophagy inH. pylorivacuolating cytotoxin A (VacA)-treated cells

Helicobacter PyloriInfection Control by Autophagy

Autophagy impairment byHelicobacter pylori-induced methylation silencing ofMAP1LC3Av1promotes gastric carcinogenesis

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