TY - JOUR
T1 - ApoB-100-containing lipoproteins are major carriers of 3-iodothyronamine in circulation
AU - Roy, Gouriprasanna
AU - Placzek, Ekaterina
AU - Scanlan, Thomas S.
PY - 2012/1/13
Y1 - 2012/1/13
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M111.275552
DO - 10.1074/jbc.M111.275552
M3 - Article
C2 - 22128163
AN - SCOPUS:84855853750
SN - 0021-9258
VL - 287
SP - 1790
EP - 1800
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 3
ER -