Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The affinity matrix prepared by the attachment of L-thyroxine (T4) to epichlorohydrine-activated Sepharose 4B biospecifically absorbs the T4-binding globulin (TBG), 25K and 80/27K proteins, immunoglobulin G (IgG) and albumin (HSA) from human normal and retroplacental sera. The absorbed protein patterns were shown to depend on the immobilized T4 concentration, pH, temperature and incubation time. The potent eluents desorbing 85-100% of the protein are 1 mM NaOH, 3 M NH4SCN, 10(-5) M T4 or 3 mM 8-anilinonaphthalene-1-sulfonic acid (ANS) for TBG; NaOH, NH4SCN, 3 mM MgCl2 or 12mM sodium cholate for 25K protein and HSA; NaOH, NH4SCN or MgCl2 for the 80/27K and 25K proteins and IgG. Moreover, T4 desorbs small amounts (6-8%) of the 80/27K and 25K proteins, while sodium cholate elutes about 6% of TBG. The eluted from T4-Sepharose 4B and further purified TBG, 25K and 80/27K proteins display different [125I]T4-binding activities within the pH range from 2 to 9 and differ by their resistance to thermal inactivation at 50-80 degrees C. Double radial immunodiffusion analysis with the use of antisera to TBG, 25K, 80/27K, HSA and IgG demonstrated that the proteins share no common antigenic determinants. It was concluded that the novel 25K and 80/27K proteins represent endogenous components of the human blood thyroid hormone-binding protein system rather than fragments or aggregates of the known T4-binding proteins.
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PMID:[Affinity chromatography of thyroxine-binding proteins from human serum]. 211 Nov 82

Iodothyronine binding to plasma lipoproteins (Lp) and gel filtration elution patterns of cholesterol and triglycerides were evaluated in the total lipoprotein fractions (TLF) obtained from 10 healthy blood donors and 7 patients with hypothyroidism of brief duration. TLF (d < 1.210 kg/L) shown to be free of plasma T4 transport proteins (TBG, TTR, HSA) was equilibrated with 0.3 nM 125I-labeled T4, T3 or reverse T3 (rT3) and chromatographed on Sepharose CL-6B. Percent distribution of rT3 among the Lp subtypes was similar in the two groups (in normals: VLDL = 4.2 +/- 2.4, LDL = 15.6 +/- 4.2, HDL = 79.9 +/- 5.2) but HDL in hypothyroid subjects bound significantly more T4 (98.7 +/- 0.4 vs. 91.2 +/- 0.3%) and T3 (95.5 +/- 2.6 vs. 78.3 +/- 11.3%). Correspondingly less T4 and T3 was bound to VLDL and LDL. Whereas rT3 elution coincided with the major HDL cholesterol peak (202 +/- 17 kDa) and was the same in the two groups, both T4 and T3 eluted with smaller HDL particles and differed between hypothyroid and normal subjects. T4 eluted with somewhat larger HDL particles in hypothyroid subjects (176 +/- 24 kDa vs. 111 +/- 34 kDa) and T3 eluted with smaller HDL (94 +/- 30 kDa vs. 148 +/- 31 kDa). The major HDL-cholesterol peak in hypothyroid subjects had a slightly but significantly greater mass than in normals (241 +/- 28 kDa vs. 218 +/- 14 kDa). The HDL elution patterns also differed: in normals there were from 3 to 6 minor peaks on either side of the major peak, whereas in hypothyroid subjects there were only 0 to 2 minor peaks. In conclusion, iodothyronines bind to relatively small size HDL subfractions and these are different for T4, T3, and rT3; hypothyroidism of brief duration induces both quantitative and qualitative changes in iodothyronine distribution among lipoproteins and alters the microheterogeneity of HDL-cholesterol.
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PMID:Altered thyroid hormone binding to plasma lipoproteins in hypothyroidism. 900 Nov 94

We have previously shown that human skin fibroblasts exposed to preformed low density lipoprotein (LDL)-thyroxine (T4) complexes internalize more T4 than they do when exposed to T4 alone. The system is set to function when the LDL receptor is up-regulated by reducing the intracellular concentration of cholesterol, and the LDL concentration outside the cell is in the range of the kDa of the receptor. High density lipoproteins (HDL), albumin (HSA), transthyretin (TTR), and thyroxine-binding globulin (TBG) interfere with, rather than facilitate, T4 entry. Of the three classes of lipoproteins (VLDL, LDL, and HDL), HDL is the major carrier of thyroid hormones. While LDL delivers cholesterol (and T4) to cells, HDL is the scavenger of cholesterol. We thus hypothesized that HDL could also facilitate thyroid hormone exit from cells. This hypothesis was tested on two human cell lines: skin fibroblasts and hepatocytes (Hep G2), using physiological concentrations of HDL or, as control, physiological concentrations of LDL, HSA, TTR, and TBG or buffer. Because cell surface receptors for HDL are regulated by intracellular cholesterol in a manner opposite to that of LDL receptors, we evaluated the effect of HDL (and other proteins) in three states: normal, high, and low intracellular cholesterol content (i.e. normal, high, and low expression of HDL receptors). In both cell lines and with either T4 or T3, we found that: 1) HDL as well as the other proteins tested increased the efflux and augmented both the initial rate of exit and the equilibrium value. 2) The efflux did not saturate over a wide range of protein concentrations. 3) The effect of HDL, LDL, and the other proteins on the fractional efflux rate of thyroid hormones remained the same irrespective of the intracellular cholesterol content (and, therefore, irrespective of the expression of either LDL or HDL receptors). 4) HSA, TTR, and TBG were, on a mass basis, equipotent and more efficient than lipoproteins. However, the effect of lipoproteins--whose Ka for T4 is comparable to that of HSA--was disproportionately high. On a molar basis, LDL (about 80% of the weight being accounted for by lipids) was more effective than HDL2 (about 60% lipids) and HDL2 was more effective than HDL3 (about 40% lipids), suggesting that the disproportionate effect of lipoproteins was due to transfer of the lypophylic thyroid hormones to the lipid moiety of lipoproteins. 5. A mixture of HDL and LDL gave the same efflux rate as a mixture of HSA, TTR, and TBG. The data indicate that the efflux of T4 and T3 from cells is rapid and appears not to be mediated by a particular lipoprotein. The disproportionately large effect of lipoproteins, which are low affinity thyroid hormone carriers, compared with nonlipoprotein carriers, and the greater effect of LDL compared with HDL, might indicate that the lipoproteins establish a nonspecific physical contact with the plasma membrane and that their hydrophobic nature favors the release of the similarly hydrophobic thyroid hormones.
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PMID:Thyroid hormone efflux from monolayer cultures of human fibroblasts and hepatocytes. Effect of lipoproteins and other thyroxine transport proteins. 975 14

Thyroxine-binding globulin (TBG), transthyretin (TTR), albumin (HSA), plus other plasmatic proteins, which include apolipoproteins, can bind and transport thyroid hormones (TH). In 1994, a 5-residue motif (Y, L/I/M, X, X, V/L/I) conserved in human TBG, TTR, HSA, and human and animal apolipoproteins was identified. Recently, we noticed that a number of residues upstream and downstream that motif are also conserved.We tested in silico the conservation of this larger motif in the many additional animal sequences of TH plasma carriers discovered after 1994. To this aim, we searched for the occurrence of the "new" motif in human and animal apolipoprotein and non-apolipoprotein TH-binding plasmatic proteins, and in a group of randomly selected proteins (2918 sequences from 56 species) not known as TH binders.Our results confirm the conservation of the "new" motif, associated with TH binding, in a total of 426 sequences analyzed (220 belonging to 169 apolipoproteins from 69 species, 206 belonging to 123 nonapolipoproteins from 54 species). Additionally, we found that within such conserved segments some differences between groups of TH plasma carriers exist. Interestingly, number and type of differences appear related to the affinity of each carrier for thyroid hormones. No occurrence of the motif was found in control proteins (alpha- and beta-tubulin, eosinophil cationic protein, endothelin-1, -2 and -3, IgG receptor, tropomyosin, Wnt inhibitory factor 1, erythropoietin, insulin and haptoglobin).Maintenance of a TH-binding domain in apolipoproteins throughout the phylum should be not less important that maintenance of the lipid binding domain.
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PMID:Conservation in the phylum of the local homology of apolipoproteins with the thyroid hormone plasma carriers. 2754 67