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

ABSTRACT

AIMS: The quorum-sensing molecule N­(3­oxododecanoyl)­l­homoserine 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: These findings indicated that C12-HSL alters mitochondrial energy production and function, and inhibits cell proliferation in LS174T cells, with PON2 involvement.