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Acta Veterinaria Scandinavica 1977The Pr protein, which is one of the major equine acidic prealbumins and which consists of a large number of phenotypes, has been studied with regard to its chemical...
The Pr protein, which is one of the major equine acidic prealbumins and which consists of a large number of phenotypes, has been studied with regard to its chemical identity. Serum samples of known Pr phenotype which had been treated with varying amounts of bovine trypsin were subjected to starch gel electrophoresis at pH 4.8. When a certain amount of trypsin was used, the Pr protein was markedly affected, whereas the other acidic prealbumins retained their normal electrophoreitic pattern. Extracts from three different regions of the acidic prealbumin field were tested by the casein precipitating inhibition test (CPI-test). Marked antitrypsin effect appeared against the extract from the Pr zone but not against the extracts from the two other acidic prealbumin zones. When acidic starch gel electrophoresis was combined with the CPI-test, a broad inhibitory zone appeared in the area of the Pr proteins. Pr protein was isolated by the use of agarose gel electrophoresis and sepharose column chromatography. The isolated protein which was tested for purity by gel electrophoresis had a molecular weight of about 60,000. It is concluded that the equine Pr protein corresponds to αi-antitrypsin.
Topics: Animals; Chemical Precipitation; Electrophoresis, Starch Gel; Horses; Phenotype; Prealbumin; Serum Albumin; Trypsin; Trypsin Inhibitors
PubMed: 596326
DOI: 10.1186/BF03548409 -
The Journal of Laboratory and Clinical... Oct 1983Amyloid deposits in several heredofamilial forms of amyloidosis are known to be chemically related to transthyretin (TTR, the plasma protein usually referred to as...
Amyloid deposits in several heredofamilial forms of amyloidosis are known to be chemically related to transthyretin (TTR, the plasma protein usually referred to as prealbumin). A genetic mutation, leading to an abnormal TTR, may be involved. Studies were conducted to investigate whether or not Portuguese patients with familial amyloidotic polyneuropathy (FAP) have an abnormal species of TTR circulating in their plasma and, if so, whether this might have any impact on vitamin A transport and retinol-binding protein (RBP) metabolism in these patients. The initial studies examined the plasma concentrations of TTR, RBP, and retinol in patients with FAP. Significantly reduced (p less than 0.005) levels of TTR were found in patients with FAP. The TTR levels in 24 FAP patients were approximately two thirds of those of a group of 18 control subjects from the same geographic area. In contrast, RBP levels were not reduced, nor was there an abnormality in the ratio of retinol to RBP, in the patients with FAP. Thus there does not appear to be an abnormality in vitamin A transport in Portuguese patients with FAP. There does, however, appear to be an abnormality of TTR metabolism, accounting for the reduced plasma levels of TTR. TTR was isolated from pooled sera of the FAP patients and was characterized in detail. FAP-TTR was indistinguishable from normal TTR with regard to a variety of parameters, including (1) electrophoretic mobility, (2) chromatographic behavior, (3) molecular weight, (4) stability of the TTR tetramer, (5) immunoreactivity in TTR radioimmunoassays using antisera prepared against both normal and FAP-TTR, (6) ability to form a protein-protein complex with RBP and affinity for RBP as assessed by polarization of fluorescence, and (7) overall amino acid composition. The possible explanations are as follows: (1) an abnormal TTR molecule is not produced in this form of FAP; (2) the abnormal molecule is present in only trace amounts (not detectable in the present study) in FAP plasma; or (3) the abnormal TTR is structurally almost identical to normal TTR and does not differ from normal TTR with regard to the various physical and chemical properties investigated in this study. Preliminary observations suggest that FAP patients do produce an abnormal form of TTR that selectively deposits in tissues as amyloid protein.
Topics: Adult; Amino Acids; Amyloidosis; Chromatography, Ion Exchange; Drug Interactions; Electrophoresis, Polyacrylamide Gel; Female; Humans; Male; Peripheral Nervous System Diseases; Portugal; Prealbumin; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma
PubMed: 6311926
DOI: No ID Found -
Rinsho Byori. the Japanese Journal of... Mar 2009Transthyretin (TTR) was previously called prealbumin because the band it formed on agarose gel electrophoresis at pH 8.6 was at the prealbumin position. However, it has... (Review)
Review
Transthyretin (TTR) was previously called prealbumin because the band it formed on agarose gel electrophoresis at pH 8.6 was at the prealbumin position. However, it has been well documented that TTR of rodents does not show a prealbumin position on electrophoresis. Now, its name describes its function, binding to retinol binding protein (RBP) and T4. The serum concentration of the protein is 20-40 mg/dl, and TTR forms a tetramer. The plasma half life of the protein is 1.9 days. TTR is synthesized by the liver, retina, pancreas, and choroid plexus. In cerebro-spinal fluid (CSF), it is the second most abundant protein, and is considered as an important protein in the pathogenesis of Alzheimer's disease, depression, and lead intoxication. In addition, TTR is a tryptophan-rich protein, it is used as one of the nutrition assessment proteins, it acts as an anti acute phase protein, and its plasma concentration decreases during inflammation and bacterial infection. Since TTR is a highly amyloidogenic protein because it contains a beta-sheet structure, it becomes a precursor protein in familial amyloidotic polyneuropathy(FAP). Moreover, TTR plays important roles in various CNS disorders, diabetes melitus, and lipid metabolism.
Topics: Alzheimer Disease; Amyloid Neuropathies, Familial; Animals; Biomarkers, Tumor; Choroid Plexus; Humans; Lipid Metabolism; Prealbumin; Protein Binding; Protein Structure, Secondary; Retinol-Binding Proteins; Thyroxine
PubMed: 19363993
DOI: No ID Found -
Clinical Transplantation Jan 2023Domino liver transplantation (DLT) has been commonly used during the last two decades to partly meet the high need for liver transplants. However, the recipients of...
BACKGROUND
Domino liver transplantation (DLT) has been commonly used during the last two decades to partly meet the high need for liver transplants. However, the recipients of grafts from patients with noncirrhotic inherited metabolic disorders may ultimately develop metabolic syndrome, and management is usually intricate, being complicated by the underlying initial disorder, other comorbidities, and post-transplantation conditions.
CASE
We report here the management and the outcome in a patient with acquired transthyretin amyloidosis after DLT and significant comorbidities. Final treatment with a transthyretin gene silencing agent, patisiran, was well tolerated and resulted in remission of the aggravating neurological deficits in a follow-up period of 2 years.
CONCLUSIONS
The case presented here supports the concept that patisiran can target the hepatocytes producing the mutated transthyretin in acquired transthyretin amyloidosis, as efficiently as in hereditary transthyretin amyloidosis (hATTR), and can be used to treat patients with transthyretin amyloidosis after DLT.
Topics: Humans; Prealbumin; Amyloid Neuropathies, Familial; Liver Transplantation
PubMed: 36128766
DOI: 10.1111/ctr.14822 -
Protein Science : a Publication of the... Jul 2018Amyloid diseases are characterized by the deposition of proteins in the form of amyloid fibrils, in organs that eventually fail. The development of effective drug...
Amyloid diseases are characterized by the deposition of proteins in the form of amyloid fibrils, in organs that eventually fail. The development of effective drug candidates follows from the understanding of the molecular processes that lead to protein aggregation. Here, we study amyloidogenic segments of transthyretin (TTR). TTR is a transporter of thyroxine and retinol in the blood and cerebrospinal fluid. When mutated and/or as a result of aging, TTR aggregates into amyloid fibrils that accumulate in organs such as the heart. Recently, we reported two amyloidogenic segments that drive amyloid aggregation. Here, we report the crystal structure of another six amyloidogenic segments of TTR. We found that the segments from the C-terminal region of TTR form in-register steric-zippers with highly-interdigitated, wet interfaces, whereas the β-strand B from the N-terminal region of TTR forms an out-of-register assembly, previously associated with oligomeric formation. Our results contribute fundamental information for understanding the mechanism of aggregation of TTR.
Topics: Amyloid; Crystallography, X-Ray; Humans; Models, Molecular; Mutation; Prealbumin; Protein Aggregates; Protein Conformation
PubMed: 29626847
DOI: 10.1002/pro.3420 -
Nature Communications Oct 2022Wild type transthyretin-derived amyloid (ATTRwt) is the major component of non-hereditary transthyretin amyloidosis. Its accumulation in the heart of elderly patients is...
Wild type transthyretin-derived amyloid (ATTRwt) is the major component of non-hereditary transthyretin amyloidosis. Its accumulation in the heart of elderly patients is life threatening. A variety of genetic variants of transthyretin can lead to hereditary transthyretin amyloidosis, which shows different clinical symptoms, like age of onset and pattern of organ involvement. However, in the case of non-hereditary transthyretin amyloidosis ATTRwt fibril deposits are located primarily in heart tissue. In this structural study we analyzed ATTRwt amyloid fibrils from the heart of a patient with non-hereditary transthyretin amyloidosis. We present a 2.78 Å reconstructed density map of these ATTRwt fibrils using cryo electron microscopy and compare it with previously published V30M variants of ATTR fibrils extracted from heart and eye of different patients. All structures show a remarkably similar spearhead like shape in their cross section, formed by the same N- and C-terminal fragments of transthyretin with some minor differences. This demonstrates common features for ATTR fibrils despite differences in mutations and patients.
Topics: Humans; Amyloid; Amyloid Neuropathies, Familial; Cryoelectron Microscopy; Prealbumin; Male; Middle Aged
PubMed: 36302762
DOI: 10.1038/s41467-022-33591-4 -
Lakartidningen Jun 2022Hereditary transthyretin (ATTRv) amyloidosis is a rare but life-threatening multi-systemic disease with clustering areas in, for example, northern Sweden. Until the...
Hereditary transthyretin (ATTRv) amyloidosis is a rare but life-threatening multi-systemic disease with clustering areas in, for example, northern Sweden. Until the 1990s, only symptomatic treatments were available but liver transplantation has, in selected patients, been a good therapeutic option since. The first disease-modifying drug for ATTRv amyloidosis was approved in 2011 and since then, the development of new therapeutic drugs has been rapid and successful. Two gene silencing therapies were approved for the disease in 2018, both showing a robust reduction in serum transthyretin levels and a satisfactory safety profile. Recently, CRISPR-Cas9 gene editing has also shown promising results in patients with ATTRv amyloidosis. The recent developments have had a paramount effect on the management of these patients, and will probably also have a significant positive effect on their life expectancy. However, treatment costs have skyrocketed, which implies future challenges.
Topics: Amyloid Neuropathies, Familial; Gene Editing; Humans; Liver Transplantation; Prealbumin
PubMed: 35670119
DOI: No ID Found -
Biochemical and Biophysical Research... Jul 1984In the serum of a Japanese patient with familial amyloidotic polyneuropathy (FAP), we demonstrated the presence of a prealbumin variant having a single amino acid...
In the serum of a Japanese patient with familial amyloidotic polyneuropathy (FAP), we demonstrated the presence of a prealbumin variant having a single amino acid substitution of a methionine residue for a valine at position 30. We have developed a highly sensitive and specific method for quantitative analysis of the prealbumin variant in the sera of FAP patients by using radioimmunoassay for a nonapeptide corresponding to subsequence [22-30] of the prealbumin variant. This peptide is produced from the prealbumin variant by cyanogen bromide cleavage followed by tryptic digestion. The serum concentration of the prealbumin variant in five Japanese FAP patients ranges from 4.0 mg/dl to 7.8 mg/dl, which is 100 times or even higher than normal controls. This method should be helpful for an early diagnosis of this hereditary disease.
Topics: Adult; Amino Acid Sequence; Amyloidosis; Genetic Variation; Humans; Japan; Male; Peptide Fragments; Peripheral Nervous System Diseases; Prealbumin; Radioimmunoassay
PubMed: 6087811
DOI: 10.1016/s0006-291x(84)80093-5 -
Clinica Chimica Acta; International... Feb 1991A sensitive ELISA method for determining transthyretin (prealbumin) in human cerebrospinal fluid (CSF) is described. The method utilizes goat antihuman transthyretin... (Comparative Study)
Comparative Study
A sensitive ELISA method for determining transthyretin (prealbumin) in human cerebrospinal fluid (CSF) is described. The method utilizes goat antihuman transthyretin antibody (IgG fraction) for capture and peroxidase conjugated antibody for color development. The assay has a linear range of 1-4 ng transthyretin added per well. The within-day and between-day coefficients of variation are 5.1 and 6.1%, respectively. The concentration of transthyretin in CSF (ranging from 5 to 20 mg per L) correlated significantly with the corresponding serum concentrations (range 170-420 mg/l). This suggests that synthesis of transthyretin in the brain and peripheral tissues is under similar biological control in normal subjects. The transthyretin concentrations in CSF did not correlate with total CSF protein concentration or age of the subject.
Topics: Adult; Aged; Enzyme-Linked Immunosorbent Assay; Humans; Male; Microchemistry; Middle Aged; Nephelometry and Turbidimetry; Prealbumin
PubMed: 2044212
DOI: 10.1016/0009-8981(91)90344-c -
The FEBS Journal Oct 2009Transthyretin is one of the three major thyroid hormone-binding proteins in plasma and/or cerebrospinal fluid of vertebrates. It transports retinol via binding to... (Review)
Review
Transthyretin is one of the three major thyroid hormone-binding proteins in plasma and/or cerebrospinal fluid of vertebrates. It transports retinol via binding to retinol-binding protein, and exists mainly as a homotetrameric protein of approximately 55 kDa in plasma. The first 3D structure of transthyretin was an X-ray crystal structure from human transthyretin. Elucidation of the structure-function relationship of transthyretin has been of significant interest since its highly conserved structure was shown to be associated with several aspects of metabolism and with human diseases such as amyloidosis. Transthyretin null mice do not have an overt phenotype, probably because transthyretin is part of a network with other thyroid hormone distributor proteins. Systematic study of the evolutionary changes of transthyretin structure is an effective way to elucidate its function. This review summarizes current knowledge about the evolution of structural and functional characteristics of vertebrate transthyretins. The molecular mechanism of evolutionary change and the resultant effects on the function of transthyretin are discussed.
Topics: Amino Acid Sequence; Animals; Apoptosis; Base Sequence; DNA; Evolution, Molecular; Humans; Models, Molecular; Molecular Sequence Data; Molecular Structure; Prealbumin; Protein Structure, Quaternary; Protein Structure, Secondary; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Thyroid Hormones; Vitamin A
PubMed: 19725883
DOI: 10.1111/j.1742-4658.2009.07243.x