Activity of ERK regulates mucin 3 expression and is involved in undifferentiated Caco-2 cell death induced by 3-oxo-C12-homoserine lactone

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2015-06, Vol.79 (6), p.937-942
• Main Authors: Shimizu, Hidehisa, Baba, Nanako, Nose, Takuma, Taguchi, Ryoko, Tanaka, Shinya, Joe, Ga-Hyun, Maseda, Hideaki, Nomura, Nobuhiko, Hagio, Masahito, Lee, Ja-Young, Fukiya, Satoru, Yokota, Atsushi, Ishizuka, Satoshi, Miyazaki, Hitoshi
• Format: Article
• Language: English
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - pharmacology; autoinducer; Caco-2 Cells; Cell Death - drug effects; Cell Differentiation - drug effects; enterobacterium; Enzyme Activation - drug effects; Homoserine - analogs & derivatives; Homoserine - pharmacology; Humans; intestine; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Mucin-3 - genetics; quorum sensing; sepsis; Up-Regulation - drug effects
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2015.1006570

The signal molecule, 3-oxo-C 12 -homoserine lactone (3-oxo-C 12 -HSL), is similar to a mammalian hormone in bacteria. Although most studies have examined the effects of high 3-oxo-C 12 -HSL concentrations (>200 μM) on mammalian cellular functions because ~600 μM 3-oxo-C 12 -HSL can be secreted in biofilms of Pseudomonas aeruginosa grown in vitro, we previously showed that a low 3-oxo-C 12 -HSL concentration (30 μM) induces the apoptosis of undifferentiated Caco-2 cells through suppressing Akt activity. Here, we found that a low concentration of 3-oxo-C 12 -HSL-activated ERK1/2 in undifferentiated Caco-2 cells. Incubating cells with the ERK pathway inhibitor U0126 for 30 min alleviated the mucin 3 (MUC3) expression suppressed by 3-oxo-C 12 -HSL, and the upregulation of MUC3 expression induced by a 48-h incubation with U0126-reduced cell death. Thus, altered MUC3 expression caused by long-term attenuated ERK1/2 activity might correlate with the death of undifferentiated Caco-2 cells induced by 3-oxo-C 12 -HSL. 3-Oxo-C12-HSL activates ERK, which suppresses MUC3 expression, and cell death induced by 3-oxo-C12-HSL depends on the amount of MUC3 expression.