title: The thyroid hormone transporters MCT8 and MCT10 transport the affinity-label N-bromoacetyl-[(125)I]T3 but are not modified by it.
abstract: Thyroid hormone (TH) transporter proteins mediate transport of TH across the plasma membrane, thereby facilitating its intracellular bioavailability. As only a few transporters have been identified which are relatively specific for TH, including monocarboxylate transporter (MCT) 8 and MCT10, the need for identification of novel specific TH transporters is obvious. A possible strategy to identify TH transporters is their modification with a ligand-derived affinity-label and subsequent identification by mass spectrometry. Previously, N-bromoacetyl (BrAc)-iodothyronines have been reported as useful affinity-labels for human (h) MCT8. In the present study we reinvestigated possible BrAc[(125)I]T3-labeling of hMCT8 and hMCT10. The present study demonstrates that hMCT8 and hMCT10 both facilitate BrAc[(125)I]T3 transport, but are not labeled by BrAc[(125)I]T3. We provide evidence that human protein disulfide isomerase, which molecular mass is similar to hMCT8, is labeled by BrAc[(125)I]T3. In addition, differential inhibitory effects were observed of iodothyronines derivatives with different side chains on T3 transport by hMCT8 and hMCT10. In conclusion, we demonstrated that not hMCT8 and hMCT10, but human protein disulfide isomerase, is labeled by BrAc[(125)I]T3. The usefulness of BrAc[(125)I]T3 as a tool for the identification of novel TH transporters remains to be explored.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Dr Molewaterplein, Rotterdam, The Netherlands. w.e.visser@erasmusmc.nl
authors.forename: W Edward
authors.initials: WE
authors.lastname: Visser
authors.forename: Alies A A
authors.initials: AA
authors.lastname: van Mullem
authors.forename: Jurgen
authors.initials: J
authors.lastname: Jansen
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
mesh_terms: D000345:Affinity Labels / Q000493:pharmacokinetics / Q000494:pharmacology*; D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism*; D027981:Symporters; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000345:Affinity Labels; D026921:Amino Acid Transport Systems, Neutral; D027501:Monocarboxylic Acid Transporters; D011994:Recombinant Proteins; C498964:SLC16A10 protein, human; C090735:SLC16A2 protein, human; D027981:Symporters; D014284:Triiodothyronine; C036219:N-bromoacetyl-3,3',5-triiodothyronine; D007453:Iodide Peroxidase; D019704:Protein Disulfide-Isomerases