BACKGROUND: @entity117 ( @entity7943 ) causes gastrotoxicity by hampering the epithelial defense against luminal contents through cyclooxygenase  inhibition. Since cell survival in tough conditions may depend on rescue mechanisms like autophagy, we analyzed whether epithelial cells rely on this process to defend themselves from @entity117 's damaging action. METHODS: @entity35 received a single dose of @entity7943 (150  mg/kg, p.o.) with or without pretreatment with the autophagy inhibitor @entity2456 , and @entity1819 and epithelial autophagy were evaluated 3  h later. The effects of @entity7943 on cell viability and autophagy were also evaluated in gastric epithelial @entity15206 cells. RESULTS: Basal autophagy in the gastric mucosa was inhibited by @entity7943 as demonstrated by increased levels of @entity28190 and ubiquitinated proteins and total @entity5615 and a reduced @entity5615 -II/ @entity5615 -I ratio. Similarly, @entity7943 increased @entity28190 and decreased @entity5615 -II accumulation and the number of EmGFP/LC3B puncta in @entity15206 cells. @entity7943 activated the PI3K/ @entity2308 -GSK3- @entity3470 pathway, which phosphorylates @entity69784 to prevent autophagy initiation, changes that were inhibited by the PI3K-inhibitor @entity2307 . Autophagy inhibition seems to enhance the vulnerability of gastric epithelial cells as a combination of @entity7943 with @entity2456 exacerbated @entity35 @entity1819 and @entity15206 cell apoptosis. CONCLUSIONS: Our data highlight the importance of autophagy in the gastric mucosa as a protective mechanism when the epithelium is injured. In the stomach, @entity117 induces @entity16 and reduces autophagy, thus, eliminating a protective mechanism that epithelial cells could use to escape @entity204 . We hypothesize that the combination of @entity117 with drugs that activate autophagy could protect against @entity1819 .

XXXX -induced gastrointestinal damage is associated with an inhibition of epithelial cell autophagy.

@entity2456 :: ('MESH:C025946', 'Chemical') :: ['3-methyladenine'] @entity2308 :: ('24185(Tax:10116)', 'Gene') :: ['Akt'] @entity5615 :: ('25291(Tax:10116)', 'Gene') :: ['LC3'] @entity69784 :: ('360827(Tax:10116)', 'Gene') :: ['ULK1'] @entity1819 :: ('MESH:D013272', 'Disease') :: ['gastric injury', 'gastric damage'] @entity117 :: ('MESH:D001241', 'Chemical') :: ['Aspirin', 'aspirin'] @entity16 :: ('MESH:D009422', 'Disease') :: ['mucosal damage'] @entity2307 :: ('MESH:C009687', 'Chemical') :: ['wortmannin'] @entity28190 :: ('117268(Tax:10116)', 'Gene') :: ['p62'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity35 :: ('10116', 'Species') :: ['rat', 'Rats'] @entity7943 :: ('D001241', 'Chemical') :: ['ASA'] @entity15206 :: ('MESH:C535607', 'Disease') :: ['AGS'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death']
@entity117 :: (MESH:D001241,Chemical) :: ['Aspirin']
