Uptake of S-(3-amino-3-oxopropyl)-cysteine by Caco-2 cells

Z Naturforsch C J Biosci. 2008 Nov-Dec;63(11-12):913-8. doi: 10.1515/znc-2008-11-1223.

Abstract

Acrylamide is a reactive neurotoxin with a high intestinal bioavailability. Recently we have shown that under the pH regime of the gut acrylamide can react with proteins and that this reaction reduces the uptake of acrylamide in a gut model. On the other hand, using radioactive labeled acrylamide, Bjellaas et al. [Toxicol. Sci. 100, 374-380 (2007)] showed that in vivo the vast majority of orally administered acrylamide is absorbed and excreted as N-acetyl-S-(3-amino-3-oxopropyl)-cysteine with the urine. Therefore, we tested whether intestinal proteases can degrade a protein with acrylamide bound to cysteine residues. Furthermore we tested whether the product of this reaction, S-(3-amino-3-oxopropyl)-cysteine, can pass the intestinal barrier. Here we showed that S-(3-amino-3-oxopropyl)-cysteine is indeed a product of proteolytic degradation of acrylamide-treated proteins. Using Caco-2 cells as a gut model, we further showed that the non-protein amino acid S-(3-amino-3-oxopropyl)-cysteine is a substrate for the neutral and cationic amino acid transporter system. Hence we concluded that protein-bound acrylamide can be released in the intestine and that the resulting product S-(3-amino-3-oxopropyl)-cysteine is transported through the intestinal barrier and later excreted via the urine.

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / metabolism
  • Acrylamide / metabolism*
  • Amino Acid Transport Systems, Acidic / metabolism*
  • Amino Acids / metabolism
  • Biological Transport
  • Caco-2 Cells / metabolism*
  • Cell Membrane Permeability
  • DNA, Neoplasm / metabolism
  • Humans
  • Kinetics
  • Protein Binding

Substances

  • Amino Acid Transport Systems, Acidic
  • Amino Acids
  • DNA, Neoplasm
  • Acrylamide
  • N-acetyl-S-(propionamide)cysteine
  • Acetylcysteine