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Titolo:
4 '-iodo-4 '-deoxydoxorubicin disrupts the fibrillar structure of transthyretin amyloid
Autore:
Palha, JA; Ballinari, D; Amboldi, N; Cardoso, I; Fernandes, R; Bellotti, V; Merlini, G; Saraiva, MJ;
Indirizzi:
Inst Mol & Cellular Biol, Amyloid Unit, P-4150 Porto, Portugal Inst Mol & Cellular Biol Porto Portugal P-4150 t, P-4150 Porto, Portugal Inst Super Ciencias Saude, Paredes, Portugal Inst Super Ciencias Saude Paredes Portugal ias Saude, Paredes, Portugal Pharmacia & Upjohn, Nerviano, Italy Pharmacia & Upjohn Nerviano ItalyPharmacia & Upjohn, Nerviano, Italy Discovery Res Oncol, Nerviano, Italy Discovery Res Oncol Nerviano ItalyDiscovery Res Oncol, Nerviano, Italy Univ Porto, Inst Ciencia Biomed Abel Salazar, P-4100 Porto, Portugal Univ Porto Porto Portugal P-4100 ed Abel Salazar, P-4100 Porto, Portugal Univ Hosp Pavia, IRCCS, Policlin San Matteo, Biotechnol Res Labs, Pavia, Italy Univ Hosp Pavia Pavia Italy n Matteo, Biotechnol Res Labs, Pavia, Italy Univ Pavia, Dept Biochem, I-27100 Pavia, Italy Univ Pavia Pavia Italy I-27100 Pavia, Dept Biochem, I-27100 Pavia, Italy
Titolo Testata:
AMERICAN JOURNAL OF PATHOLOGY
fascicolo: 6, volume: 156, anno: 2000,
pagine: 1919 - 1925
SICI:
0002-9440(200006)156:6<1919:4''DTF>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-FIBRILLOSES; THIOFLAVINE-T; DEPOSITS; POLYNEUROPATHY; ANTHRACYCLINE; PREALBUMIN; DISEASE; LIVER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Saraiva, MJ Inst Mol & Cellular Biol, Amyloid Unit, Rua Campo Alegre 823, P-4150 Porto, Portugal Inst Mol & Cellular Biol Rua Campo Alegre 823 PortoPortugal P-4150
Citazione:
J.A. Palha et al., "4 '-iodo-4 '-deoxydoxorubicin disrupts the fibrillar structure of transthyretin amyloid", AM J PATH, 156(6), 2000, pp. 1919-1925

Abstract

Transthyretin (TTR) is a tetrameric protein synthesized mainly by the liver and the choroid plexus, from where it is secreted into the plasma and thecerebrospinal fluid, respectively, Some forms of polyneuropathy, vitreopathy, and cardiomyopathy are caused by the deposition of normal and/or mutantTTR molecules in the form of amyloid fibrils. Familial amyloidotic polyneuropathy is the most common form of TTR amyloidosis related to the V30M variant. It is still unclear the process by which soluble proteins deposit as amyloid. The treatment of amyloid-related disorders might attempt the stabilization of the soluble protein precursor to retard or inhibit its deposition as amyloid; or aim at the resorption of the deposited amyloid. The anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX) has been shown to reduce the amyloid load in immunoglobulin light-chain amyloidosis, We investigated 1) whether I-DOX has affinity for TTR amyloid in tissues, 2) determined the I-DOX binding constants to TTR synthetic fibrils, and 3) determined the nature of the effect of I-DOX on TTR fibrils. We report that 1) I-DOX co-localizeswith amyloid deposits in tissue sections of patients with familial amyloidotic polyneuropathy; 2) I-DOX strongly interacts with TTR amyloid fibrils and presents two binding sites with k(d) of 1.5 x 10(-11) mol/L and 5.6 x 10(-10) mol/L, respectively; and 3) I-DOX disrupts the fibrillar structure ofTTR amyloid into amorphous material, as assessed by electron microscopy but does not solubilize the fibrils as confirmed by filter assays. These datasupport the hypothesis that I-DOX and less toxic derivatives can prove efficient in, the treatment of TTR-related amyloidosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 12:08:50