| Characterization of the binding of thyroxine to high density lipoproteins and apolipoproteins A-I. | |
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MedLine Citation:
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PMID: 2498379 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We studied binding of T4 to the lipid-complexed apolipoproteins (apo) of high density lipoproteins (HDL), the major lipoprotein carrier of thyroid hormones in human plasma, and to lipid-free apoA-I. HDL isolated from fresh normal plasma by ultracentrifugation (density, 1.063-1.210 g/mL) was photoaffinity labeled with [3,5-(125)I]T4 and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two bands corresponding to apoA-I (28.3K) and apoC-II or apoC-III (8.6-9.2K) were seen, and their radioactivity decreased by 50-60% when labeled in the presence of 1 mumol/L T4. Photoaffinity labeling of isolated apoA-I also was demonstrated and was decreased 74% by 1 mumol/L T4, suggesting a higher affinity of the lipid-free protein for T4. T4 binding of isolated apoA-I was optimal at pH 7-8, reached a maximum after 1 h at 23 C, and decreased after incubation at 37 C. Scatchard analysis revealed a single T4-binding site with a Ka of 7.5 x 10(7) L/mol at 23 C, pH 8.2. The potency of T4 analogs as inhibitors of T4 binding to isolated apoA-I was L-T4 = D-T4 = triiodothyroacetic acid = L-rT3 much greater than L-T3 much greater than L-thyronine. The binding of T4 to apoA-I was reduced by known inhibitors of T4 binding to serum proteins (diclofenac = mefenamic acid = furosemide = 8-anilinonaphthalene sulfonic acid much greater than dilantin greater than heparin greater than barbital) and by lipids (unsaturated fatty acids greater than cholesterol = cholesterol esters = phospholipids greater than saturated fatty acids = diglycerides = triglycerides). We conclude that the binding of T4 to HDL is mediated by a specific interaction of the hormone with apoA-I and with apoC-II and/or apoC-III. Since the lipid constituents of HDL inhibit T4 binding to apoA-I, the HDL subfraction in plasma that carries most of the HDL-bound T4 should be one with a low lipid content. |
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Authors:
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S Benvenga; H J Cahnmann; R E Gregg; J Robbins |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 68 ISSN: 0021-972X ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 1989 Jun |
Date Detail:
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Created Date: 1989-06-30 Completed Date: 1989-06-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1067-72 Citation Subset: AIM; IM |
Affiliation:
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Clinical Endocrinology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apolipoprotein A-I Apolipoproteins A / analysis* Autoradiography Binding Sites / drug effects Diclofenac / pharmacology Furosemide / pharmacology Lipoproteins, HDL / analysis* Lipoproteins, VLDL / analysis Mefenamic Acid / pharmacology Temperature Thyroid Hormones / blood Thyroxine / analysis* Thyroxine-Binding Proteins / analysis* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein A-I; 0/Apolipoproteins A; 0/Lipoproteins, HDL; 0/Lipoproteins, VLDL; 0/Thyroid Hormones; 0/Thyroxine-Binding Proteins; 15307-86-5/Diclofenac; 54-31-9/Furosemide; 61-68-7/Mefenamic Acid; 7488-70-2/Thyroxine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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