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

• DOI: 10.1016/j.lfs.2018.03.049
• Publication Date: 2018-03-27T04:09:21Z
• Authors: Shiyu Tao; Liqiong Niu; Liuping Cai; Yali Geng; Canfeng Hua; Yingdong Ni; Ruqian Zhao
• Keywords: 0301 basic medicine; 0303 health sciences; Aryldialkylphosphatase; Quorum Sensing; Apoptosis; 7. Clean energy; Mitochondria; 3. Good health; Electron Transport; Intestines; 03 medical and health sciences; Adenosine Triphosphate; 4-Butyrolactone; Homoserine; Humans; Calcium; Goblet Cells; Cell Proliferation

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.