Helicobacter pylori‐downregulated tumor necrosis factor receptor‐associated protein 1 mediates apoptosis of human gastric epithelial cells

Heat shock proteins (HSPs) are crucial proteins in maintaining the homeostasis of human gastric epithelial cells. Tumor necrosis factor receptor‐associated protein 1 (TRAP1), a member of the HSP90 family, has been shown to be involved in various crucial physiological processes, particularly against...

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Veröffentlicht in:Journal of cellular physiology 2019-09, Vol.234 (9), p.15698-15707
Hauptverfasser: Teng, Yongsheng, Liu, Xin, Han, Bin, Ma, Qiang, Liu, Yugang, Kong, Hui, Lv, Yipin, Mao, Fangyuan, Cheng, Ping, Hao, Chuanjie, Yang, Shiming, Zhang, Jinyu, Peng, Liusheng, Zou, Quanming, Zhuang, Yuan
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container_end_page 15707
container_issue 9
container_start_page 15698
container_title Journal of cellular physiology
container_volume 234
creator Teng, Yongsheng
Liu, Xin
Han, Bin
Ma, Qiang
Liu, Yugang
Kong, Hui
Lv, Yipin
Mao, Fangyuan
Cheng, Ping
Hao, Chuanjie
Yang, Shiming
Zhang, Jinyu
Peng, Liusheng
Zou, Quanming
Zhuang, Yuan
description Heat shock proteins (HSPs) are crucial proteins in maintaining the homeostasis of human gastric epithelial cells. Tumor necrosis factor receptor‐associated protein 1 (TRAP1), a member of the HSP90 family, has been shown to be involved in various crucial physiological processes, particularly against apoptosis. However, the regulation and function of TRAP1 in Helicobacter pylori infection is still unknown. Here, we found that TRAP1 expression was downregulated on human gastric epithelial cells during H. pylori infection by real‐time polymerase chain reaction (PCR) and western blot analysis. Through virulence factors mutant H. pylori strains infection and inhibitors screening, we found that H. pylori vacuolating cytotoxin A ( vacA), but not cytotoxin‐associated gene A ( cagA) protein, induced human gastric epithelial cells to downregulate TRAP1 via P38MAPK pathway by real‐time PCR and western blot analysis. Furthermore, downregulation of TRAP1 with lentivirus carrying TRAP1 short hairpin RNA constructs impairs mitochondrial function, and increases apoptosis of gastric epithelial cells. The results indicate that H. pylori vacA downregulated TRAP1 is involved in the regulation of gastric epithelial cell apoptosis. Helicobacter pylori vacA‐induced gastric epithelial cells to downregulate tumor necrosis factor receptor‐associated protein 1 (TRAP1) via P38MAPK pathway. Downregulated TRAP1 expression impairs mitochondrial function and increases of activated (cleaved) caspase‐3 expression, which results in an increased apoptosis of gastric epithelial cells.
doi_str_mv 10.1002/jcp.28223
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Tumor necrosis factor receptor‐associated protein 1 (TRAP1), a member of the HSP90 family, has been shown to be involved in various crucial physiological processes, particularly against apoptosis. However, the regulation and function of TRAP1 in Helicobacter pylori infection is still unknown. Here, we found that TRAP1 expression was downregulated on human gastric epithelial cells during H. pylori infection by real‐time polymerase chain reaction (PCR) and western blot analysis. Through virulence factors mutant H. pylori strains infection and inhibitors screening, we found that H. pylori vacuolating cytotoxin A ( vacA), but not cytotoxin‐associated gene A ( cagA) protein, induced human gastric epithelial cells to downregulate TRAP1 via P38MAPK pathway by real‐time PCR and western blot analysis. Furthermore, downregulation of TRAP1 with lentivirus carrying TRAP1 short hairpin RNA constructs impairs mitochondrial function, and increases apoptosis of gastric epithelial cells. The results indicate that H. pylori vacA downregulated TRAP1 is involved in the regulation of gastric epithelial cell apoptosis. Helicobacter pylori vacA‐induced gastric epithelial cells to downregulate tumor necrosis factor receptor‐associated protein 1 (TRAP1) via P38MAPK pathway. Downregulated TRAP1 expression impairs mitochondrial function and increases of activated (cleaved) caspase‐3 expression, which results in an increased apoptosis of gastric epithelial cells.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.28223</identifier><identifier>PMID: 30710368</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Apoptosis ; Epithelial cells ; gastric epithelial cells ; Heat shock proteins ; Helicobacter pylori ; Homeostasis ; Hsp90 protein ; Infections ; Mitochondria ; Necrosis ; Polymerase chain reaction ; Proteins ; Ribonucleic acid ; RNA ; TRAP1 ; Tumor necrosis factor ; Tumor necrosis factor-TNF ; Tumors ; vacA ; Virulence ; Virulence factors</subject><ispartof>Journal of cellular physiology, 2019-09, Vol.234 (9), p.15698-15707</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4193-b7a168c880026ec4b20c0fff663e32537d1ac7b9aabc7729cc1e30d95b6de89d3</citedby><cites>FETCH-LOGICAL-c4193-b7a168c880026ec4b20c0fff663e32537d1ac7b9aabc7729cc1e30d95b6de89d3</cites><orcidid>0000-0001-7825-0032</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.28223$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.28223$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30710368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teng, Yongsheng</creatorcontrib><creatorcontrib>Liu, Xin</creatorcontrib><creatorcontrib>Han, Bin</creatorcontrib><creatorcontrib>Ma, Qiang</creatorcontrib><creatorcontrib>Liu, Yugang</creatorcontrib><creatorcontrib>Kong, Hui</creatorcontrib><creatorcontrib>Lv, Yipin</creatorcontrib><creatorcontrib>Mao, Fangyuan</creatorcontrib><creatorcontrib>Cheng, Ping</creatorcontrib><creatorcontrib>Hao, Chuanjie</creatorcontrib><creatorcontrib>Yang, Shiming</creatorcontrib><creatorcontrib>Zhang, Jinyu</creatorcontrib><creatorcontrib>Peng, Liusheng</creatorcontrib><creatorcontrib>Zou, Quanming</creatorcontrib><creatorcontrib>Zhuang, Yuan</creatorcontrib><title>Helicobacter pylori‐downregulated tumor necrosis factor receptor‐associated protein 1 mediates apoptosis of human gastric epithelial cells</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>Heat shock proteins (HSPs) are crucial proteins in maintaining the homeostasis of human gastric epithelial cells. Tumor necrosis factor receptor‐associated protein 1 (TRAP1), a member of the HSP90 family, has been shown to be involved in various crucial physiological processes, particularly against apoptosis. However, the regulation and function of TRAP1 in Helicobacter pylori infection is still unknown. Here, we found that TRAP1 expression was downregulated on human gastric epithelial cells during H. pylori infection by real‐time polymerase chain reaction (PCR) and western blot analysis. Through virulence factors mutant H. pylori strains infection and inhibitors screening, we found that H. pylori vacuolating cytotoxin A ( vacA), but not cytotoxin‐associated gene A ( cagA) protein, induced human gastric epithelial cells to downregulate TRAP1 via P38MAPK pathway by real‐time PCR and western blot analysis. Furthermore, downregulation of TRAP1 with lentivirus carrying TRAP1 short hairpin RNA constructs impairs mitochondrial function, and increases apoptosis of gastric epithelial cells. 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The results indicate that H. pylori vacA downregulated TRAP1 is involved in the regulation of gastric epithelial cell apoptosis. Helicobacter pylori vacA‐induced gastric epithelial cells to downregulate tumor necrosis factor receptor‐associated protein 1 (TRAP1) via P38MAPK pathway. Downregulated TRAP1 expression impairs mitochondrial function and increases of activated (cleaved) caspase‐3 expression, which results in an increased apoptosis of gastric epithelial cells.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30710368</pmid><doi>10.1002/jcp.28223</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7825-0032</orcidid></addata></record>
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subjects Apoptosis
Epithelial cells
gastric epithelial cells
Heat shock proteins
Helicobacter pylori
Homeostasis
Hsp90 protein
Infections
Mitochondria
Necrosis
Polymerase chain reaction
Proteins
Ribonucleic acid
RNA
TRAP1
Tumor necrosis factor
Tumor necrosis factor-TNF
Tumors
vacA
Virulence
Virulence factors
title Helicobacter pylori‐downregulated tumor necrosis factor receptor‐associated protein 1 mediates apoptosis of human gastric epithelial cells
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