Transthyretin: the servant of many masters

Buxbaum, Joel N.; Reixach, Natàlia

doi:10.1007/s00018-009-0109-0

Cited by 182 publications

(168 citation statements)

References 65 publications

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“…The nitrocellulose membrane was blocked for 1 h with 5% non-fat dried milk in tris-buffered saline (TBS) and incubated with primary antibody against TG (Sigma, St. Louis, MO, USA)/TTR (Abcam, USA) at 37 • C for 2 h. The blots were washed six times for 30 min with tris-buffered saline Tween-20 (TBST) and then incubated with AP-conjugated secondary antibody at 37 • C for 1 h. After that the blots were washed six times again, they were developed using a BCIP/NBT Kit (AMRESCO, USA). TTR is considered as an evolutionarily conserved serum protein (Hennebry et al, 2006;Buxbaum and Reixach, 2009 (Morgado et al, 2007). Using a rabbit antihuman TG serum that cross-reacted with lampreys (Lampetra appendix) TG, Western blotting detected a single protein of ∼226 kDa (Manzon and Youson, 2002).…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

Bioconcentration and metabolism of decabromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae

et al. 2012

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Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

Bioconcentration and metabolism of decabromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae

et al. 2012

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“…Studies have shown that TTR forms amyloid through a process that is initiated by tetramer destabilization. The destabilization results in accumulation of monomers, which can misfold and aggregate into fibrillar structures (11). Considerable effort has been devoted to studying the amyloidogenicity of TTR mutations related to the familial forms of the disease, though the majority of TTR-related amyloidosis is represented by sporadic cases caused by aggregation and deposition of the otherwise stable WT protein.…”

mentioning

confidence: 99%

Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein

Noborn

O’Callaghan

Hermansson

et al. 2011

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

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Transthyretin (TTR) is a homotetrameric protein that transports thyroxine and retinol. Tetramer destabilization and misfolding of the released monomers result in TTR aggregation, leading to its deposition as amyloid primarily in the heart and peripheral nervous system. Over 100 mutations of TTR have been linked to familial forms of TTR amyloidosis. Considerable effort has been devoted to the study of TTR aggregation of these mutants, although the majority of TTR-related amyloidosis is represented by sporadic cases due to the aggregation and deposition of the otherwise stable wild-type (WT) protein. Heparan sulfate (HS) has been found as a pertinent component in a number of amyloid deposits, suggesting its participation in amyloidogenesis. This study aimed to investigate possible roles of HS in TTR aggregation. Examination of heart tissue from an elderly cardiomyopathic patient revealed substantial accumulation of HS associated with the TTR amyloid deposits. Studies demonstrated that heparin/HS promoted TTR fibrillization through selective interaction with a basic motif of TTR. The importance of HS for TTR fibrillization was illustrated in a cell model; TTR incubated with WT Chinese hamster ovary cells resulted in fibrillization of the protein, but not with HS-deficient cells (pgsD-677). The effect of heparin on TTR fibril formation was further demonstrated in a Drosophila model that overexpresses TTR. Heparin was colocalized with TTR deposits in the head of the flies reared on heparin-supplemented medium, whereas no heparin was detected in the nontreated flies. Heparin of low molecular weight (Klexane) did not demonstrate this effect.systemic amyloidosis | sulfated glycosaminoglycans | aging | heart failure

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“…HUVECs were incubated with WT and V30M TTR tetramers at the final concentration of 4 M for 3 h. We chose this concentration because it is the one that resembles the plasma levels of TTR ϳ25 mg/dl (17,26). Changes in mRNA expression are given as -fold changes comparing V30M TTR versus WT TTR-treated cells.…”

Section: Differential Response Of Ecs To V30m Ttr Compared With Wt Ttrmentioning

confidence: 99%

Transthyretin Proteins Regulate Angiogenesis by Conferring Different Molecular Identities to Endothelial Cells

Nunes

Oliveira

Lages

et al. 2013

Journal of Biological Chemistry

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Familial amyloidotic polyneuropathy (FAP) has a high prevalence in Portugal, and the most common form of hereditary amyloidosis is caused by an amyloidogenic variant of transthyretin (TTR) with a substitution of methionine for valine at position 30 (V30M). Until now, the available efficient therapy is liver transplantation, when performed in an early phase of the onset of the disease symptoms. However, transplanted FAP patients have a significantly higher incidence of early hepatic artery thrombosis compared with non-FAP transplanted patients. Because FAP was described as an independent risk factor for early hepatic artery thrombosis, more studies to understand the underlying mechanisms involved in this outcome are of the utmost importance. Knowing that the liver is the major site for TTR production, we investigated the biological effects of TTR proteins in the vasculature and on angiogenesis. In this study, we identified genes differentially expressed in endothelial cells exposed to the WT or V30M tetramer. We found that endothelial cells may acquire different molecular identities when exposed to these proteins, and consequently TTR could regulate angiogenesis. Moreover, we show that V30M decreases endothelial survival by inducing apoptosis, and it inhibits migration. These findings provide new knowledge that may have critical implications in the prevention of early hepatic artery thrombosis in FAP patients after liver transplantation

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Transthyretin: the servant of many masters

Cited by 182 publications

References 65 publications

Bioconcentration and metabolism of decabromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae

Bioconcentration and metabolism of decabromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae

Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein

Transthyretin Proteins Regulate Angiogenesis by Conferring Different Molecular Identities to Endothelial Cells

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