Disease relevance of Ttr

• The decrease in transcription of the transthyretin gene in liver, which is characteristic for the acute phase response, was overridden by stimulation of gene expression after partial hepatectomy [1].
• The amino acid sequence of rabbit prealbumin was determined by analyses of peptides obtained by trypsin and Staphylococcus aureus protease digestions [2].
• Combined proteomic approach with SELDI-TOF-MS and peptide mass fingerprinting identified the rapid increase of monomeric transthyretin in rat cerebrospinal fluid after transient focal cerebral ischemia [3].
• A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes [4].
• Transthyretin was bound by human hepatoma (Hep G2) cells in a time- and temperature-dependent manner, reaching equilibrium within 2 h [5].

Psychiatry related information on Ttr

• Here we present evidence that the receptor for advanced glycation end products (RAGE), previously associated with Alzheimer's disease, acts as a selective cell surface acceptor site for both soluble and fibrillar TTR [6].
• Rat transthyretin: effects of acute short-term food deprivation and refeeding on serum and cerebrospinal fluid concentration and on hepatic mRNA level [7].

High impact information on Ttr

• HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the genes for transthyretin (TTR), the carrier protein in the serum for vitamin A and thyroid hormone, and for apolipoprotein CIII (apoCIII), a major constituent of chylomicrons and very low-density lipoproteins (VLDL) [8].
• Unlike its association with low vitamin A level in the liver, the lesion could be seen even in the presence of normal serum values of vitamin A, retinol binding protein, and prealbumin [9].
• Immunocytochemical studies on the localization of plasma and of cellular retinol-binding proteins and of transthyretin (prealbumin) in rat liver and kidney [10].
• Pulse-chase experiments in conjunction with subcellular fractionation and quantitative immunoprecipitation have been used to study the intracellular transport of four secretory proteins, albumin, transferrin, prealbumin and retinol-binding protein, in isolated rat hepatocytes [11].
• In aged rats fed throughout life with PUFA-enriched diets, genes with altered expressions included transthyretin, alpha-synuclein, and calmodulins, which play important roles in synaptic plasticity and learning [12].

Chemical compound and disease context of Ttr

• Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis [13].
• According to recent studies on protein chemistry and genetic engineering, replacement of the Val30 residue of prealbumin by methionine is believed to play a critical role in the formation of amyloid deposit and the pathogenesis of familial amyloidotic polyneuropathy (FAP) [14].
• Retinol-binding protein (RBP) and transthyretin (TTR) in the plasma, liver and kidney, retinol in plasma, and total vitamin A in the liver were measured in rats 6 weeks after diabetes mellitus had been induced by streptozotocin (STZ) [15].
• In contrast, no effect of hypothyroidism or T3 replacement on hepatic levels of thyroxine binding prealbumin mRNA was demonstrated, indicating the specificity of thyroid hormone action [16].
• To investigate the regulation of genes whose expression is enriched in liver we studied expression of the albumin and transthyretin (TTR) genes in a series of rat hepatoma cell lines (FaO, C2, C2rev7, and H5) that express these genes at different rates [17].

Biological context of Ttr

• Presumptive choroid plexus cells in the inner lining of the neural tube expressed transthyretin early in gestation (11 days before birth) with a maximum immediately preceding the spurt of brain growth around birth [1].
• Both amino acid sequences contain 127 amino acid residues, the same as human prealbumin [2].
• Using specific cDNA probes, tissue specificity and regulation of transthyretin mRNA biosynthesis during embryogenesis were analyzed [1].
• Transthyretin cDNA was isolated from a rat liver cDNA library [18].
• The rat transthyretin gene, 7.3 kilobase pairs (kb) long, with 14.5 kb of 5' flanking and 12.2 kb of 3' flanking region was cloned and characterized [1].

Anatomical context of Ttr

• This stimulation also affected transthyretin expression in choroid plexus [1].
• Both retinol-binding protein mRNA and transthyretin mRNA in the visceral yolk sac were found to be specifically localized in the endodermal layer [19].
• Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus [20].
• Retinol-binding protein mRNA and transthyretin mRNA were both detected in the liver of fetuses at 14 days of gestation [19].
• Immunoreactive TTR was localized in cells that were more centrally distributed in the islets, with an anatomic distribution that resembled that of the insulin-containing B cells [21].

Associations of Ttr with chemical compounds

• Region with linkage to serum concentrations of cholesterol (probably located beyond the terminal marker Ttr of the linkage group) were also found [22].
• Amyloidogenicity of rat TTR from rats with or without challenging paraquat was compared in vitro by thioflavin T test [23].
• Complex of rat transthyretin with tetraiodothyroacetic acid refined at 2.1 and 1.8 A resolution [24].
• We believe the beneficial effects of fish oil might be common to other agents, i.e., induce TTR expression, like nicotine and Ginkgo biloba extract [20].
• Plasma and cellular retinoid-binding proteins and transthyretin (prealbumin) are all localized in the islets of Langerhans in the rat [21].

Physical interactions of Ttr

• Effect of hypothyroidism and thyroid hormone treatment of the rat on hepatic Spot 14 and thyroxine binding prealbumin mRNAs [16].

Regulatory relationships of Ttr

• Transthyretin mRNA is expressed in abundance in the primordial CP epithelium prior to CP morphogenesis (e10-11) but IGF-II mRNA expression begins later (e13) and increases gradually as morphogenesis proceeds [25].
• Both turpentine injection and CLP increased expression of TNFalpha/IL-1beta-regulated alpha1-acid glycoprotein, and IL-6-regulated alpha2-macroglobulin and decreased expression of transthyretin (a negative acute phase protein) [26].

Other interactions of Ttr

• Transthyretin mRNA was found only in the liver and in the choroid plexus, but not in other parts of the central nervous system nor in the adrenal glands, kidney, spleen, testes, heart, lung, intestine, and ovaries [18].
• Differential expression of the insulin-like growth factor II and transthyretin genes in the developing rat choroid plexus [25].
• Conversely, negative acute-phase reactants are reduced on inflammation: alpha1-inhibitor III, alpha2-HS-glycoprotein, kallikrein-binding protein and transthyretin (all reduced to between 1/2 to 1/3 of the baseline levels), retinol-binding protein (to about 1/2 to 1/4) and albumin (to 2/3) [27].
• Among the negative APP, neither albumin nor prealbumin decreased while CBG increased [28].
• Amino-acid compositional and sequence analyses as well as mass spectrometric determinations of purified rat urine proteins, previously termed prealbumin and alpha(2)-euglobulin, have revealed a high homology between the two forms which have now been identified as alpha(2)-globulin species [29].

Analytical, diagnostic and therapeutic context of Ttr

• Rat transthyretin (prealbumin). Molecular cloning, nucleotide sequence, and gene expression in liver and brain [18].
• Oligodeoxynucleotide affinity chromatography (with one of the TTR binding sites) allowed a 500-fold purification of the protein [4].
• The transcription of transthyretin (TTR) was induced by 10-fold as evidenced by microarray analysis and confirmed by real-time quantitative RT-PCR [20].
• Total RNA, prepared from the isolated stellate cells, was examined by Northern blot analysis for retinol-binding protein mRNA and transthyretin mRNA, using cDNA probes for retinol-binding protein and transthyretin [30].
• Stellate cell homogenates were assayed for both retinol-binding protein and transthyretin by specific radioimmunoassays [30].

References