title: Mitigating endoplasmic reticulum stress with revaprazan ameliorates stress-related mucosal disease.
abstract: OBJECTIVE
  The term "stress-related mucosal disease" (SRMD) represents conditions ranging from superficial mucosal damage to focal deep mucosal damage in the stomach, of which pathogenesis is deduced to be violent mucosal ischemia or excess oxidative stress, but not fully clarified yet. Under the hypothesis that mucosal cell apoptosis subsequent to endoplasmic reticulum (ER) stress might play a crucial role, we evaluated the efficacy and mechanism that novel acid pump antagonist (APA), revaprazan, alleviated water immersion restraint stress (WIRS) induced SRMD in rats.
  
  
  METHODS
  In order to define whether WIRS-induced SRMD is associated with ER stress, we checked the alteration in the expression of ER stress markers including GRP78, CHOP, XBP-1, BiP as well as apoptosis in WIRS-induced SRMD. The efficacy of revaprazan on either alleviating ER stress or attenuating SRMD was compared with proton pump inhibitor (PPI) and gastroprotectant.
  
  
  RESULTS
  Ten hours of WIRS induced a severe degree of SRMD, in which ER stress markers including CHOP, XBP1, and BiP were significantly overexpressed in the gastric tissues. However, these markers of ER stress were significantly decreased in the group pretreated with revaprazan compared to PPI or gastroprotectant, accompanied with a significant reduction in apoptotic index. In addition to ER stress, revaprazan imposed anti-inflammatory benefit to limit SRMD based on significant levels of inflammatory cell apoptosis.
  
  
  CONCLUSIONS
  Endoplasmic reticulum stress accompanied with drastic apoptosis was implicated in the development of SRMD, but revaprazan could rescue the stomach from SRMD through alleviating ER stress in epithelial cells much better than either PPI or gastroprotectant.
authors: Department of Gastroenterology Gil Medical Center, Gachon Graduate School of Medicine, Incheon, Korea.
authors: Jung Ho
authors: JH
authors: Kim
authors: Eun Hee
authors: EH
authors: Kim
authors: Chanyoung
authors: C
authors: Ock
authors: Hua
authors: H
authors: Hong
authors: Yoon Jae
authors: YJ
authors: Kim
authors: Kwang An
authors: KA
authors: Kwon
authors: Dong Kyun
authors: DK
authors: Park
authors: Ki Baik
authors: KB
authors: Hahm
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D019610:Cytoprotection; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005753:Gastric Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D007101:Immersion; D018836:Inflammation Mediators / Q000378:metabolism; D050217:Metabolic Detoxication, Phase II; D051379:Mice; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000071701:Regulatory Factor X Transcription Factors; D012720:Severity of Illness Index; D013272:Stomach Diseases / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological / Q000187:drug effects*; D013315:Stress, Psychological / Q000150:complications*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000071717:X-Box Binding Protein 1
chemical_list: D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; C497251:Ddit3 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C051684:GRP78 protein, rat; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018836:Inflammation Mediators; D054328:Proton Pump Inhibitors; D011744:Pyrimidinones; D000071701:Regulatory Factor X Transcription Factors; D044005:Tetrahydroisoquinolines; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; C000605545:Xbp1 protein, rat; D051742:Transcription Factor CHOP; C108798:YH 1885