Uptake of S-(3-amino-3-oxopropyl)-cysteine by Caco-2 cells.
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.
Schwend
Thomas
T
Institut für Pharmazie und Molekulare Biotechnologie, Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
Schabacker
Jens
J
Wetterauer
Bernhard
B
Wink
Michael
M
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D020106:Acrylamide / Q000378:metabolism*; D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D001692:Biological Transport; D018938:Caco-2 Cells / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004273:DNA, Neoplasm / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011485:Protein Binding
D026922:Amino Acid Transport Systems, Acidic; D000596:Amino Acids; D004273:DNA, Neoplasm; D020106:Acrylamide; C085597:N-acetyl-S-(propionamide)cysteine; D000111:Acetylcysteine