Thyroid Hormone Binding by Human Serum Prealbumin (TBPA). ELECTROPHORETIC STUDIES OF TRIIODOTHYRONINE-TBPA INTERACTION

Davis, Paul J.; Handwerger, Barry S.; Gregerman, Robert I.

doi:10.1172/jci106839

Cited by 44 publications

(7 citation statements)

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“…TTR is a major serum thyroid hormone binding protein with a molecular mass of 14 kDa [10] which was formerly known as thyroxine-binding prealbumin protein. It was first recognized to bind thyroxine (T4) in 1958 [11] and subsequently shown that TTR also binds to retinol-binding protein and thus plays a role in the transport of vitamin A [12] , [13] .Thus, the name was changed to transthy(roxin)retin(ol) for denoting its dual transport function [14] . Plasma TTR is synthesized by the hepatic parenchymal cells while in fetal life it is synthesized by the yolk sac of endothelium [15] .…”

Section: Introductionmentioning

confidence: 99%

Identification of Autoantibodies against Transthyretin for the Screening and Diagnosis of Rheumatoid Arthritis

et al. 2014

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Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic and inflammatory rheumatic disease that leads to inflammation of the joints and surrounding tissues. Identification of novel protein(s) associated with severity of RA is a prerequisite for better understanding of pathogenesis of this disease that may also have potential to serve as novel biomarkers in the diagnosis of RA. Present study was undertaken to compare the amount of autoantigens and autoantibodies in the plasma of RA patients in comparison to healthy controls. Plasma samples were collected from the patients suffering from RA, Osteoarthritis (OA), Systemic lupus erythematosus (SLE) and healthy volunteers. The screening of plasma proteins were carried out using 2-dimensional gel electrophoresis followed by identification of differentially expressed protein by MALDI-TOF MS/MS. Among several differentially expressed proteins, transthyretin (TTR) has been identified as one of the protein that showed significantly up regulated expression in the plasma of RA patients. The results were further validated by Western blot analysis and ELISA. In comparison to OA synovium, an exclusive significantly high expression of TTR in RA has been validated through IHC, Western blotting and IEM studies. Most importantly, the increase in expression of TTR with the progression of severity of RA condition has been observed. The autoantibodies against TTR present in the RA plasma were identified using immunoprecipitation-Western methods. The significant production of autoantibodies was validated by ELISA and Western blot analysis using recombinant pure protein of TTR. Hence, these novel observations on increase in TTR expression with the increase in severity of RA conditions and significant production of autoantibodies against TTR clearly suggest that a systematic studies on the role TTR in the pathogenesis of RA is immediately required and TTR may be used as a serum diagnostic marker together with other biochemical parameters and clinical symptoms for RA screening and diagnosis.

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Section: Introductionmentioning

confidence: 99%

Identification of Autoantibodies against Transthyretin for the Screening and Diagnosis of Rheumatoid Arthritis

et al. 2014

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“…[125I]T4 was purchased from Amersham and its purity verified by thin layer chromatography (8). 45Ca was obtained from ICN Radioisotopes (Cambridge, MA).…”

Section: Methodsmentioning

confidence: 99%

Milrinone and thyroid hormone stimulate myocardial membrane Ca2+-ATPase activity and share structural homologies.

Mylotte¹,

Cody²,

Davis³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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We have recently shown that thyroid hormone in physiological concentrations stimulates sarcolemmaenriched rabbit-myocardial-membrane Ca2+-ATPase in vitro. In this study, milrinone [2-methyl-5-cyano-(3,4'-bipyridin Ca2+-ATPase. Amrinone [5-amino-(3,4'-bipyridin)-6(1H)-one], the parent bipyridine of milrinone, had no effect on myocardial Ca2+-ATPase activity. X-ray crystallographic analysis of milrinone and amrinone revealed structural homologies between the phenolic ring of thyroxine and the substituted ring of milrinone, whereas amrinone did not share these homologies. The mechanism(s) of the inotropic actions of thyroxine and of milrinone is not clearly understood, but these observations implicate Ca2+-ATPase, a calcium pump-associated enzyme, as one mediator ofthe effects on the heart ofthese two compounds.Milrinone [2-methyl-5-cyano-(3,4'-bipyridin)-6(1H)-one] is a nonglycosidic positive-inotropic bipyridine (1, 2) whose biochemical mechanism of action on the heart has not been -established. The action of the bipyridines could involve either phosphodiesterase inhibition and cyclic AMP accumulation (3)(4)(5) or increasing the rate of calcium sequestration (6). The drug has a bipyridine structure whose substituted ring has features that might mimic those of the thyroid hormones, thyroxine (T4) or triiodothyronine (T3); this caused us to examine milrinone for stimulatory action on rabbit myocardial membrane Ca2+-ATPase activity. We have previously reported that physiological concentrations of thyroxine (0.10 nM) stimulate this myocardial membrane calcium pump-associated enzyme in vitro via a calmodulin-dependent process (7). This Ca2+-ATPase is thought to be responsible for calcium ejection by myocardial cells during rest.

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“…1 Part of a report read at the Sixth International Thyroid Conference, Vienna, June 1970. members without the trait. All 24 subjects were clinically euthyroid and had no history of thyroid disease or drug treatment.…”

Section: Subjectsmentioning

confidence: 99%

“…Three bindingproteins have been identified: thyroxinebinding globulin (TBG), thyroxine-binding pre-albumin (TBPA) and albumin. TBG, being the major transport protein, carries about 55 to 75% of the TT 4 (1,2). In subjects with inherited TBG deficiency, low TT 4 values and high percentages of free thyroxine (FT 4 ) are found in the blood.…”

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confidence: 99%

Relationship Between Total Thyroxine and Absolute Free Thyroxine and the Influence of Absolute Free Thyroxine on Thyroxine Disposal in Humans¹

Hennemann¹,

Docter²,

Dolman³

1971

The Journal of Clinical Endocrinology & Metabolism

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Studies were conducted concerning the relation between TT< and AFT 4 in a family with TBG deficiency, consisting of 8 affected and 16 unaffected members, and in a group of 48 normals. A highly significant positive relationship between these 2 parameters was found within the family, as well as within the group of normals. Subjects with TBG deficiency had low TT 4 and lowered AFT4 levels. From additional studies it appeared that there existed no relationship between AFT 4 and T 4 disposal in 20 euthyroid controls, including 2 subjects with TBG deficiency and 2 females with TBG elevation due to oral contraceptives. It is concluded that in these circumstances AFT 4 was not a clear determinant in the absolute peripheral T 4 turnover. (J Clin Endocr 33: 63, 1971)

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Thyroid Hormone Binding by Human Serum Prealbumin (TBPA). ELECTROPHORETIC STUDIES OF TRIIODOTHYRONINE-TBPA INTERACTION

Abstract: A B S T R A C T Thyroxine-binding prealbumin (TBPA) in normal human serum has been shown in a polyacrylamide gel electrophoresis system to bind 7-9% of tracer level purified ['I]

Cited by 44 publications

References 20 publications

Identification of Autoantibodies against Transthyretin for the Screening and Diagnosis of Rheumatoid Arthritis

Identification of Autoantibodies against Transthyretin for the Screening and Diagnosis of Rheumatoid Arthritis

Milrinone and thyroid hormone stimulate myocardial membrane Ca2+-ATPase activity and share structural homologies.

Relationship Between Total Thyroxine and Absolute Free Thyroxine and the Influence of Absolute Free Thyroxine on Thyroxine Disposal in Humans¹

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Thyroid Hormone Binding by Human Serum Prealbumin (TBPA). ELECTROPHORETIC STUDIES OF TRIIODOTHYRONINE-TBPA INTERACTION

Abstract: A B S T R A C T Thyroxine-binding prealbumin (TBPA) in normal human serum has been shown in a polyacrylamide gel electrophoresis system to bind 7-9% of tracer level purified ['I]

Cited by 44 publications

References 20 publications

Identification of Autoantibodies against Transthyretin for the Screening and Diagnosis of Rheumatoid Arthritis

Identification of Autoantibodies against Transthyretin for the Screening and Diagnosis of Rheumatoid Arthritis

Milrinone and thyroid hormone stimulate myocardial membrane Ca2+-ATPase activity and share structural homologies.

Relationship Between Total Thyroxine and Absolute Free Thyroxine and the Influence of Absolute Free Thyroxine on Thyroxine Disposal in Humans1

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Relationship Between Total Thyroxine and Absolute Free Thyroxine and the Influence of Absolute Free Thyroxine on Thyroxine Disposal in Humans¹