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Helicobacter pylori VacA induces autophagic cell death in gastric epithelial cells via the endoplasmic reticulum stress pathway.
Cell Death Dis. 2017 12 13; 8(12):3207.CD

Abstract

The Helicobacter pylori vacuolating cytotoxin (VacA) can promote progressive vacuolation and gastric injury and may be associated with human gastric cancer. Increasing evidence indicates that autophagy is involved in the cell death induced by VacA, but the specific mechanisms need to be further elucidated. We show here that VacA could induce autophagy and increase cell death in human gastric cancer cell lines. Further investigations revealed that inhibition of autophagy could decrease the VacA-induced cell death in AGS cells. Furthermore, numerous dilated endoplasmic reticula (ER) were observed, and the phosphorylation of a subunit of eukaryotic translation initiation factor 2 subunit 1 also increased in the VacA-treated AGS cells, while repression of ER stress could reduce autophagy and cell death through knockdown of activating transcription factor 4 and DNA-damage-inducible transcript 3. In addition, the expression of pseudokinase tribbles homolog 3 (TRIB3) upon ER stress was triggered by VacA, and knockdown of TRIB3 could also decrease VacA-induced cell death. Finally, inhibition of autophagy could decrease VacA s1m1 -induced cell death and apoptosis, and apoptosis inhibitor Z-VAD had no significant effect on autophagy induced by VacA s1m1 . Thus, these results suggested that VacA causes autophagic cell death via ER stress in gastric epithelial cells.

Authors+Show Affiliations

Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China.Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China.Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China.Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China.Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China.Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China.Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China.Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China.Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China. mxh95xy@tom.com.Department of Clinical Microbiology and Immunology, Southwest Hospital and College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, China. tangbin811012@163.com. Emei Sanatorium of PLA Rocket Force, Emeishan, 614205, China. tangbin811012@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29238039

Citation

Zhu, Pan, et al. "Helicobacter Pylori VacA Induces Autophagic Cell Death in Gastric Epithelial Cells Via the Endoplasmic Reticulum Stress Pathway." Cell Death & Disease, vol. 8, no. 12, 2017, p. 3207.
Zhu P, Xue J, Zhang ZJ, et al. Helicobacter pylori VacA induces autophagic cell death in gastric epithelial cells via the endoplasmic reticulum stress pathway. Cell Death Dis. 2017;8(12):3207.
Zhu, P., Xue, J., Zhang, Z. J., Jia, Y. P., Tong, Y. N., Han, D., Li, Q., Xiang, Y., Mao, X. H., & Tang, B. (2017). Helicobacter pylori VacA induces autophagic cell death in gastric epithelial cells via the endoplasmic reticulum stress pathway. Cell Death & Disease, 8(12), 3207. https://doi.org/10.1038/s41419-017-0011-x
Zhu P, et al. Helicobacter Pylori VacA Induces Autophagic Cell Death in Gastric Epithelial Cells Via the Endoplasmic Reticulum Stress Pathway. Cell Death Dis. 2017 12 13;8(12):3207. PubMed PMID: 29238039.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Helicobacter pylori VacA induces autophagic cell death in gastric epithelial cells via the endoplasmic reticulum stress pathway. AU - Zhu,Pan, AU - Xue,Jun, AU - Zhang,Zhu-Jun, AU - Jia,Yin-Ping, AU - Tong,Ya-Nan, AU - Han,Dan, AU - Li,Qian, AU - Xiang,Yang, AU - Mao,Xu-Hu, AU - Tang,Bin, Y1 - 2017/12/13/ PY - 2016/12/16/received PY - 2017/10/02/accepted PY - 2017/09/25/revised PY - 2017/12/15/entrez PY - 2017/12/15/pubmed PY - 2018/7/19/medline SP - 3207 EP - 3207 JF - Cell death & disease JO - Cell Death Dis VL - 8 IS - 12 N2 - The Helicobacter pylori vacuolating cytotoxin (VacA) can promote progressive vacuolation and gastric injury and may be associated with human gastric cancer. Increasing evidence indicates that autophagy is involved in the cell death induced by VacA, but the specific mechanisms need to be further elucidated. We show here that VacA could induce autophagy and increase cell death in human gastric cancer cell lines. Further investigations revealed that inhibition of autophagy could decrease the VacA-induced cell death in AGS cells. Furthermore, numerous dilated endoplasmic reticula (ER) were observed, and the phosphorylation of a subunit of eukaryotic translation initiation factor 2 subunit 1 also increased in the VacA-treated AGS cells, while repression of ER stress could reduce autophagy and cell death through knockdown of activating transcription factor 4 and DNA-damage-inducible transcript 3. In addition, the expression of pseudokinase tribbles homolog 3 (TRIB3) upon ER stress was triggered by VacA, and knockdown of TRIB3 could also decrease VacA-induced cell death. Finally, inhibition of autophagy could decrease VacA s1m1 -induced cell death and apoptosis, and apoptosis inhibitor Z-VAD had no significant effect on autophagy induced by VacA s1m1 . Thus, these results suggested that VacA causes autophagic cell death via ER stress in gastric epithelial cells. SN - 2041-4889 UR - https://www.unboundmedicine.com/medline/citation/29238039/Helicobacter_pylori_VacA_induces_autophagic_cell_death_in_gastric_epithelial_cells_via_the_endoplasmic_reticulum_stress_pathway_ L2 - https://doi.org/10.1038/s41419-017-0011-x DB - PRIME DP - Unbound Medicine ER -