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

Biosci Biotechnol Biochem. 2015;79(6):937-42. doi: 10.1080/09168451.2015.1006570. Epub 2015 Mar 16.

Abstract

The signal molecule, 3-oxo-C12-homoserine lactone (3-oxo-C12-HSL), is similar to a mammalian hormone in bacteria. Although most studies have examined the effects of high 3-oxo-C12-HSL concentrations (>200 μM) on mammalian cellular functions because ~600 μM 3-oxo-C12-HSL can be secreted in biofilms of Pseudomonas aeruginosa grown in vitro, we previously showed that a low 3-oxo-C12-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-C12-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-C12-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-C12-HSL.

Keywords: autoinducer; enterobacterium; intestine; quorum sensing; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / pharmacology
  • Caco-2 Cells
  • Cell Death / drug effects
  • Cell Differentiation / drug effects
  • Enzyme Activation / drug effects
  • Homoserine / analogs & derivatives*
  • Homoserine / pharmacology
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Mucin-3 / genetics*
  • Up-Regulation / drug effects*

Substances

  • Mucin-3
  • N-(3-oxododecanoyl)homoserine lactone
  • Homoserine
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • 4-Butyrolactone