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

Author:
Tao, Shiyu, Niu, Liqiong, Cai, Liuping, Geng, Yali, Hua, Canfeng, Ni, Yingdong, Zhao, Ruqian
Source:
Life sciences 2018 v.201 pp. 81-88
ISSN:
0024-3205
Subject:
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
Abstract:
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.
Agid:
5925586