Document Detail

Characterization of the binding of thyroxine to high density lipoproteins and apolipoproteins A-I.
MedLine Citation:
PMID:  2498379     Owner:  NLM     Status:  MEDLINE    
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.
S Benvenga; H J Cahnmann; R E Gregg; J Robbins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  1989-06-30     Completed Date:  1989-06-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1067-72     Citation Subset:  AIM; IM    
Clinical Endocrinology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892.
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MeSH Terms
Apolipoprotein A-I
Apolipoproteins A / analysis*
Binding Sites / drug effects
Diclofenac / pharmacology
Furosemide / pharmacology
Lipoproteins, HDL / analysis*
Lipoproteins, VLDL / analysis
Mefenamic Acid / pharmacology
Thyroid Hormones / blood
Thyroxine / analysis*
Thyroxine-Binding Proteins / analysis*
Time Factors
Reg. No./Substance:
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

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