Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1.
The short-chain fatty acid butyrate was readily taken up by Caco-2 cells. Transport exhibited saturation kinetics, was enhanced by low extracellular pH, and was Na(+) independent. Butyrate uptake was unaffected by DIDS; however, alpha-cyano-4-hydroxycinnamate and the butyrate analogs propionate and L-lactate significantly inhibited uptake. These results suggest that butyrate transport by Caco-2 cells is mediated by a transporter belonging to the monocarboxylate transporter family. We identified five isoforms of this transporter, MCT1, MCT3, MCT4, MCT5, and MCT6, in Caco-2 cells by PCR, and MCT1 was found to be the most abundant isoform by RNase protection assay. Transient transfection of MCT1, in the antisense orientation, resulted in significant inhibition of butyrate uptake. The cells fully recovered from this inhibition by 5 days after transfection. In conclusion, our data showed that the MCT1 transporter may play a major role in the transport of butyrate into Caco-2 cells.
Hadjiagapiou
C
C
Section of Digestive and Liver Diseases, Department of Medicine, University of Illinois at Chicago and the West Side Veterans Affairs Medical Center, Chicago, Illinois 60612, USA.
Schmidt
L
L
Dudeja
P K
PK
Layden
T J
TJ
Ramaswamy
K
K
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002087:Butyrates / Q000378:metabolism*; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007773:Lactates / Q000494:pharmacology; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D011422:Propionates / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D027981:Symporters; D014162:Transfection
D002087:Butyrates; D002352:Carrier Proteins; D007773:Lactates; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D011422:Propionates; D020033:Protein Isoforms; D011994:Recombinant Proteins; C106260:SLC16A3 protein, human; C406962:SLC16A4 protein, human; D027981:Symporters; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid