ApoB-100-containing lipoproteins are major carriers of 3-iodothyronamine in circulation

Abstract

3-Iodothyronamine (T 1AM) is a biogenic amine derivative of thyroid hormone present in tissue and blood of vertebrates. Approximately 99% of the circulating thyroid hormones are bound to plasma proteins, including three major thyroid hormone-binding proteins, and the question arises as to whether circulating T 1AM is also bound to serum factors. We report here that T 1AM is largely bound to a single protein component of human serum. Using T 1AM-affinity chromatography, we isolated this protein, and sequence analysis identified it as apolipoprotein B-100 (apoB-100), the protein component of several low density lipoprotein particles. Consistent with this finding, we demonstrate that >90% of specifically bound T 1AM in human serum resides in the apoB-100-containing low density lipoprotein fraction. T 1AM reversibly binds to apoB-100-containing lipoprotein particles with an equilibrium dissociation constant (K D) of 17 nM and a T 1AM/apoB-100 stoichiometry of 1:1. Competition binding assays demonstrate that this binding site is highly selective for T 1AM. Intracellular T 1AM uptake is significantly enhanced by apoB-100-containing lipoprotein particles. Modest enhancements to apoB-100 cellular uptake and secretion by T 1AM were observed; however, multidose T 1AM treatment did not affect lipid or lipoprotein inventory in vivo. Thus, it appears that apoB-100 serves as a carrier of circulating T 1AM and affords a novel mechanism by which T 1AM gains entry to cells. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.