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Titolo:
Pathogenesis of beta(2)-microglobulin amyloidosis
Autore:
Ohashi, K;
Indirizzi:
Tokyo Metropolitan Komagome Hosp, Dept Pathol, Bunkyo Ku, Tokyo 1130021, Japan Tokyo Metropolitan Komagome Hosp Tokyo Japan 1130021 okyo 1130021, Japan
Titolo Testata:
PATHOLOGY INTERNATIONAL
fascicolo: 1, volume: 51, anno: 2001,
pagine: 1 - 10
SICI:
1320-5463(200101)51:1<1:POBA>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
LONG-TERM HEMODIALYSIS; GLYCATION END-PRODUCTS; AMINO-ACID-SEQUENCE; HIGH-AFFINITY BINDING; TUMOR-NECROSIS-FACTOR; ACUTE-PHASE REACTANT; ALZHEIMERS-DISEASE; ENHANCING FACTOR; P-COMPONENT; PRECURSOR PROTEIN;
Keywords:
amyloidosis; beta(2)-microglobulin; chondroitin sulfate; extracellular matrix; hemodialysis; heparan sulfate; matrix metalloproteinases; proteoglycans;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
101
Recensione:
Indirizzi per estratti:
Indirizzo: Ohashi, K Tokyo Metropolitan Komagome Hosp, Dept Pathol, Bunkyo Ku, 3-18-22 Honkomagome, Tokyo 1130021, Japan Tokyo Metropolitan Komagome Hosp 3-18-22 Honkomagome Tokyo Japan 1130021
Citazione:
K. Ohashi, "Pathogenesis of beta(2)-microglobulin amyloidosis", PATHOL INT, 51(1), 2001, pp. 1-10

Abstract

Hemodialysis-related amyloidosis is a relatively new form of systemic amyloidosis, with beta (2)-microglobulin (B2M) being identified as the major constituent protein. Most of the clinical findings are related to amyloid deposition in osseo-articular tissues. B2M amyloid deposits first appear in the cervical intervertebral discs, which are well known to be susceptible to mechanical stress. A close relationship between changes of microenvironmentcaused by such stress and amyloid deposition is highly suggested. In advanced cases, an inflammatory reaction composed of macrophages, multinucleatedgiant cells, and granulation tissue, is observed around the amyloid deposits. Purified amyloid protein is native B2M, and mutations and proteolysis are not believed to be important for its deposition. Plasma levels of B2M are elevated as much as 5-10 times because of the inability of hemodialysis equipment removal of B2M from blood plasma, the duration being very important for B2M amyloid fibrillogenesis. Heparan sulfate proteoglycans, perlecan,is increased at the same sites of amyloid deposits from the early stages. In B2M amyloidosis, an increase of heparan sulfate proteoglycans is observed in the vascular wall and synovium, but in the discs, ligaments and cartilage, there is an increase of chondroitin sulfate proteoglycans predominantly. B2M has an affinity for heparan sulfate proteoglycans, although it is weaker than that for laminin and type IV collagen. This is related to the interactions between negative charges of sulfate groups of proteoglycans and positive charges of basic amino acids in N-terminal side of B2M. Increased cytokines production in the synovium, induced by advanced glycation end products as well as elevated plasma levels, is also linked to inflammatory reactions. Increased expression of matrix metalloproteinases (MMP), especially MMP-1 and -9, is related to the destructive changes of the bone and cartilage. The decrease of plasma levels by high flux membrane and control of inflammatory reactions are very important for prevention of B2M amyloidosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 15:35:08