title: Paraoxonase 2 modulates a proapoptotic function in LS174T cells in response to quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone.
abstract: A mucus layer coats the gastrointestinal tract and serves as the first line of intestinal defense against infection. N-acyl-homoserine lactone (AHL) quorum-sensing molecules produced by gram-negative bacteria in the gut can influence the homeostasis of intestinal epithelium. In this study, we investigated the effects of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)-homoserine lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on cell viability and mucus secretion in LS174T cells. C12-HSL but not C4-HSL significantly decreased cell viability by inducing mitochondrial dysfunction and activating cell apoptosis which led to a decrease in mucin expression. Pretreatment with lipid raft disruptor (Methyl-β-cyclodextrin, MβCD) and oxidative stress inhibitor (N-acetyl-L-cysteine, NAC) slightly rescued the viability of cells damaged by C12-HSL exposure, while the paraoxonase 2 (PON2) inhibitor (Triazolo[4,3-a]quinolone, TQ416) significantly affected recovering cells viability and mucin secretion. When LS174T cells were treated with C12-HSL and TQ416 simultaneously, TQ416 showed the maximal positive effect on cells viability. However, if cells were first treated with C12-HSL for 40 mins, and then TQ46 was added, the TQ416 had no effect on cell viability. These results suggest that the C12-HSL-acid process acts at an early step to activate apoptosis as part of C12-HSL's effect on intestinal mucus barrier function.
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Tao
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, China.
authors.lastname: Bin He
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT 05452, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Qian
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, China.
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Key Laboratory of Animal Physiology &Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, China.
authors.forename: Ruqian
authors.initials: R
authors.lastname: Zhao
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism; D053038:Quorum Sensing; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: C524625:MUC2 protein, human; D055262:Mucin-2; C109860:N-(3-oxododecanoyl)homoserine lactone; C092312:N-butyrylhomoserine lactone; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D006714:Homoserine; D043303:Aryldialkylphosphatase; D015107:4-Butyrolactone; D000111:Acetylcysteine