title: Pyrrolidine dithiocarbamate restores gastric damages and suppressive autophagy induced by hydrogen peroxide.
abstract: It is well known that gastric barrier is very important for protecting host from various insults. Simultaneously, autophagy serving as a prominent cytoprotective and survival pathway under oxidative stress conditions is being increasingly recognized. Thus, this study was conducted for investigating the effect of pyrrolidine dithiocarbamate (PDTC) on gastric barrier function and autophagy under oxidative stress induced by intragastric administration of hydrogen peroxide (H2O2). The gastric tight junction proteins [zonula occludens-1 (ZO1), occludin, and claudin1], autophagic proteins [microtubule-associated protein light chain 3I(LC3I), LC3II, and beclin1], and nuclear factor kappa B (NF-κB) signaling pathway (p65 and IκB kinase α/β) were determined by Western blot. The results showed that H2O2 exposure disturbed gastric barrier function with decreased expression of ZO1, occludin, and claudin1, and reduced gastric autophagy with decreased conversion of LC3I into LC3II in mice. However, treatment with PDTC restored these adverse effects evidenced by increased expression of ZO1 and claudin1 and increased conversion of LC3I into LC3II. Meanwhile, H2O2 exposure decreased normal human gastric epithelial mucosa cell line (GES-1) viability in a concentration-dependent way. However, after being exposed to H2O2, GES-1 exhibited autophagic response which was inconsistent with our in vivo results in mice, while PDTC failed to decrease autophagy in GES-1 induced by H2O2. Simultaneously, the beneficial effect of PDTC on gastric damage and autophagy in mice might be independent of inhibition of NF-κB. In conclusion, PDTC treatment restores gastric damages and reduced autophagy induced by H2O2. Therefore, PDTC may serve as a potential adjuvant therapy for gastric damages.
authors.affiliation: Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences , Changsha, Hunan , P. R. China.
authors.forename: J L
authors.initials: JL
authors.lastname: Duan
authors.forename: J
authors.initials: J
authors.lastname: Yin
authors.forename: W K
authors.initials: WK
authors.lastname: Ren
authors.forename: M M
authors.initials: MM
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Cui
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: R L
authors.initials: RL
authors.lastname: Huang
authors.forename: T J
authors.initials: TJ
authors.lastname: Li
authors.forename: Y L
authors.initials: YL
authors.lastname: Yin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D013859:Thiocarbamates / Q000494:pharmacology*; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D062725:Tight Junction Proteins; C020972:pyrrolidine dithiocarbamic acid; D006861:Hydrogen Peroxide; D051550:I-kappa B Kinase
keywords: autophagy; hydrogen peroxide; oxidative stress; pyrrolidine dithiocarbamate; tight junction protein