Mucin 3 is involved in intestinal epithelial cell apoptosis via N-(3-oxododecanoyl)-L-homoserine lactone-induced suppression of Akt phosphorylation.
N-acyl-homoserine lactones (AHL) are quorum-sensing molecules in bacteria that play important roles in regulating virulence gene expression in pathogens such as Pseudomonas aeruginosa. The present study compared responses between undifferentiated and differentiated Caco-2 cells to N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL). A low concentration of 3-oxo-C12-HSL (30 μM) is sufficient to reduce viability accompanied by apoptosis via the suppression of phosphorylation by Akt in undifferentiated Caco-2 cells. The suppression of Akt phosphorylation appears specific in 3-oxo-C12-HSL, because other AHLs did not influence the phosphorylation status of Akt. The reduced viability induced by 3-oxo-C12-HSL was partially recovered by constitutively active Akt overexpression in undifferentiated Caco-2 cells. Since mucin is considered a vital component of the gut barrier, we investigated whether mucin protects cellular functions induced by 3-oxo-C12-HSL in undifferentiated Caco-2 cells. The results showed that mucin protected undifferentiated Caco-2 cells from apoptosis induced by 3-oxo-C12-HSL. 3-Oxo-C12-HSL did not induce cell death in differentiated Caco-2 cells that expressed higher levels of mucin 3 (MUC3) than undifferentiated Caco-2 cells. In addition, 3-oxo-C12-HSL promoted cell death in undifferentiated Caco-2 cells transfected with MUC3 siRNA and reduced MUC3 expression in undifferentiated Caco-2 cells. Therefore, MUC3 might be responsible for the survival of undifferentiated intestinal epithelial cells in the presence of 3-oxo-C12-HSL through regulating Akt phosphorylation. In conclusion, 3-oxo-C12-HSL might influence the survival of undifferentiated intestinal epithelial cells as well as interactions between these cells and pathogens.
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan;
Ryoko
R
Taguchi
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan;
Shinya
S
Tanaka
Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan;
Ga-Hyun
GH
Joe
Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan; and.
Hideaki
H
Maseda
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan;
Nobuhiko
N
Nomura
Department of Food and Nutrition, Tokyo Kasei University, Tokyo, Japan.
Junji
J
Ohnishi
Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan;
Satoshi
S
Ishizuka
Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan;
Hidehisa
H
Shimizu
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan; miyazaki.hitoshi.gb@u.tsukuba.ac.jp.
Hitoshi
H
Miyazaki
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D055263:Mucin-3 / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D055263:Mucin-3; C109860:N-(3-oxododecanoyl)homoserine lactone; D006714:Homoserine; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D015107:4-Butyrolactone
autoinducer; enterobacterium; intestine; quorum sensing; sepsis