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N-(3-oxododecanoyl)-l-homoserine lactone modulates mitochondrial function and suppresses proliferation in intestinal goblet cells

Tao, Shiyu, Niu, Liqiong, Cai, Liuping, Geng, Yali, Hua, Canfeng, Ni, Yingdong, Zhao, Ruqian
Life sciences 2018 v.201 pp. 81-88
Pseudomonas aeruginosa, adenosine triphosphate, animal pathogenic bacteria, apoptosis, aryldialkylphosphatase, calcium, cell cycle checkpoints, cell proliferation, electron transport chain, energy, enzyme-linked immunosorbent assay, flow cytometry, genes, goblet cells, mammals, mitochondria, quantitative polymerase chain reaction, quorum sensing, viability
The quorum-sensing molecule N‑(3‑oxododecanoyl)‑l‑homoserine lactone (C12-HSL), produced by the Gram negative human pathogenic bacterium Pseudomonas aeruginosa, modulates mammalian cell behavior. Our previous findings suggested that C12-HSL rapidly decreases viability and induces apoptosis in LS174T goblet cells.In this study, the effects of 100 μM C12-HSL on mitochondrial function and cell proliferation in LS174T cells treated for 4 h were evaluated by real-time PCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry.The results showed that the activities of mitochondrial respiratory chain complexes IV and V were significantly increased (P < 0.05) in LS174T cells after C12-HSL treatment, with elevated intracellular ATP generation (P < 0.05). Flow cytometry analysis revealed significantly increased intracellular Ca²⁺ levels (P < 0.05), as well as disrupted mitochondrial activity and cell cycle arrest upon C12-HSL treatment. Apoptosis and cell proliferation related genes showed markedly altered expression levels (P < 0.05) in LS174T cells after C12-HSL treatment. Moreover, the paraoxonase 2 (PON2) inhibitor TQ416 (1 μM) remarkably reversed the above C12-HSL associated effects in LS174T cells.These findings indicated that C12-HSL alters mitochondrial energy production and function, and inhibits cell proliferation in LS174T cells, with PON2 involvement.