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Abstract
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 < 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.
Abbreviations:
transthyretin ((TTR)), retinol-binding protein ((RBP)), familial amyloidotic polyneuropathy ((FAP)), normal TTR ((N-TTR)), TTR from patients with FAP ((FAP-TTR)), sodium dodecyl sulfate ((SDS)), polyacrylamide gel electrophoresis ((PAGE)), blood urea nitrogen ((BUN)), diethylaminoethyl ((DEAE))To read this article in full you will need to make a payment
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References
- The amino acid sequence of human plasma prealbumin.J Biol Chem. 1974; 249: 6796
- Structure of human plasma prealbumin at 2.5 Å resolution. A preliminary report on the polypeptide chain conformation, quaternary structure and thyroxine binding.J Mol Biol. 1974; 88: 1
- Structure of prealbumin. Secondary, tertiary, and quaternary interactions determined by Fourier refinement at 1.8 Å.J Mol Biol. 1978; 121: 339
- Negative cooperativity in the binding of thyroxine to human serum prealbumin.Biochemistry. 1975; 14: 282
- The interaction of human plasma retinol-binding protein with prealbumin.J Biol Chem. 1973; 248: 4698
- The interaction between retinol-binding proteins and prealbumins studied by fluorescence polarization.Biochim Biophys Acta. 1976; 439: 449
- The effects of diseases of the liver, thyroid, and kidneys on the transport of vitamin A in human plasma.J Clin Invest. 1971; 50: 2426
- Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy.in: ed. 3. Proc Natl Acad Sci USA. 75. 1978: 4499
- Amyloid fibril protein in type I familial amyloidotic polyneuropathy in Japanese.J Lab Clin Med. 1981; 98: 811
- Amyloid in hereditary amyloid polyneuropathy is related to prealbumin.Arch Neurol. 1981; 38: 420
- Partial amino acid sequence homology between an heredofamilial amyloid protein and human plasma prealbumin.J Clin Invest. 1981; 67: 1035
- The prealbumin nature of the amyloid protein in familial amyloid polyneuropathy (FAP)—Swedish variety.Biochem Biophys Res Commun. 1981; 99: 1326
- A variant of prealbumin from amyloid fibrils in familial polyneuropathy of Jewish origin.J Exp Med. 1981; 154: 989
- A peculiar form of peripheral neuropathy: familial atypical generalized amyloidosis with special involvement of the peripheral nerves.Brain. 1952; 75: 408
- Familial amyloidotic polyneuropathy.in: Wegelius O Pasternack A Amyloidosis. Academic Press, Inc, New York1976: 183-193
- Retinol-binding protein: the transport protein for vitamin A in human plasma.J Clin Invest. 1968; 47: 2025
- The interaction of thyroxine with human plasma prealbumin and with the prealbumin-retinol binding protein complex.J Biol Chem. 1969; 244: 3230
- Studies on the interaction between prealbumin, retinol-binding protein, and vitamin A.J Biol Chem. 1971; 246: 44
- Disc electrophoresis. II. Method and application to human serum proteins.Ann NY Acad Sci. 1964; 121: 404
- Disc electrophoresis in polyacrylamide gels: extension to new conditions of pH and buffer.Ann NY Acad Sci. 1964; 121: 373
- The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide electrophoresis.J Biol Chem. 1969; 244: 4406
- Cleavage of structural proteins during the assembly of the head of bacteriophage T4.Nature. 1970; 227: 680
- Use of particulate immunosorbents in radioimmunoassay.Methods Enzymol. 1981; 73: 203
- Salt fractionation of immunoglobulins.in: ed. 3. Handbook of Experimental Immunology. vol. 1. Blackwell Scientific Publications, Oxford1978 (chap. 7)
- A simple chromatographic method for preparation of gamma globulin.in: ed. 6. Proc Soc Exp Biol Med. 103. 1960: 250
- Protein iodination with solid state lactoperoxidase.Biochemistry. 1974; 13: 1014
- Partial amino acid sequence of human retinol-binding protein. Isolation and alignment of the five cyanogen bromide fragments and the amino acid sequences of 4 of the fragments.J Lipid Res. 1979; 20: 865
- Retinoid affinity label for the binding site of retinol-binding protein.Biochemistry. 1982; 21: 1899
- Fluorescence studies of human plasma retinol-binding protein and of the retinol-binding protein-prealbumin complex.Biochim Biophys Acta. 1972; 260: 670
- Apparatus for use in the chromatography of amino acids.Anal Chem. 1958; 30: 1190
- Immunochemical quantitation of antigens by single radial immunodiffusion.Immunochemistry. 1965; 2: 235
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem. 1976; 72: 248
- Simultaneous determination of α-tocopherol and retinol in plasma or red cells by high pressure liquid chromatography.Am J Clin Nutr. 1979; 32: 2143
- Statistical Methods.ed. 6. Iowa State University Press, Ames, Iowa1967
- Plasma vitamin A transport and visual dark adaptation in diseases of the intestine and liver.Scand J Clin Lab Invest. 1978; 38: 301
- Demonstration in serum of two physiological forms of the human retinol-binding protein.Eur J Clin Invest. 1971; 1: 437
- Demonstration of human prealbumins by double one dimensional slab gel electrophoresis.Electrophoresis. 1981; 2: 148
- Prealbumin: antigenic properties in the Portuguese type of amyloid neuropathy, Presented at 1st Iberian Congress of Biochemistry. Abst. P-334. 1980
- Thyroxine-binding prealbumin. Conformation in aqueous solutions.J Biol Chem. 1971; 246: 6011
- Amyloid deposits and amyloidosis.N Engl J Med. 1980; 302: 1283
- Immunologic and immunohistochemical study of familial amyloid polyneuropathy.Neurology. 1981; 31: 1493
- Senile cerebral amyloid. Prealbumin as a common constituent in the neuritic plaque, in the neurofibrillary tangle, and in the microangiopathic lesion.Am J Pathol. 1982; 107: 41
- Senile cardiac amyloid is related to prealbumin.Scand J Immunol. 1980; 12: 503
- Senile cardiac amyloid: evidence that fibrils contain a protein immunologically related to prealbumin.Immunology. 1981; 44: 447
- Depressed serum prealbumin levels in patients with familial amyloid polyneuropathy (FAP) and their non-affected relatives.Arthritis Rheum. 1982; 25: S58
- Prealbumin and retinol binding protein levels in heredofamilial amyloidosis.Clin Res. 1982; 30: 788A
- Plasma vitamin A, retinol-binding protein, and prealbumin concentration in protein-calorie malnutrition. III. Response to varying dietary treatments.Am J Clin Nutr. 1975; 28: 732
- Immunochemically determined serum prealbumin in hepatitis in children.Arch Immunol Ther Exp. 1975; 23: 53
- Primary structure of an amyloid prealbumin variant in familial polyneuropathy of Jewish origin.in: Proc Natl Acad Sci USA. 801. 1983: 539
- Presence of an abnormal transthyretin (prealbumin) in Portuguese patients with familial amyloidotic polyneuropathy.Clin Res. 1983; 31: 533A
Article info
Publication history
Accepted:
June 7,
1983
Received:
March 1,
1983
Footnotes
☆This work was supported by NIH grants HL-21006 (SCOR) and AM-05968.
Identification
Copyright
© 1983 Published by Elsevier Inc.
