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Titolo:
A deficiency of cysteine impairs fibrillin-1 deposition: Implications for the pathogenesis of cystathionine beta-synthase deficiency
Autore:
Majors, AK; Pyeritz, RE;
Indirizzi:
MCP Hahnemann Sch Med, Dept Human Genet, Pittsburgh, PA 15212 USA MCP Hahnemann Sch Med Pittsburgh PA USA 15212 t, Pittsburgh, PA 15212 USA
Titolo Testata:
MOLECULAR GENETICS AND METABOLISM
fascicolo: 4, volume: 70, anno: 2000,
pagine: 252 - 260
SICI:
1096-7192(200008)70:4<252:ADOCIF>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
MARFAN-SYNDROME; PLASMA HOMOCYSTEINE; HOMOCYSTINURIA; COLLAGEN; MUTATIONS; MICROFIBRILS; COMPONENT; DISEASE; THIOLS; GENE;
Keywords:
fibrillin; cysteine; homocysteine; cystathionine; beta-synthase; homocystinuria; extracellular matrix; Marfan syndrome;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Majors, AK Cleveland Clin Fdn, Dept Cell Biol, Lerner Res Inst, NC10,9500 Euclid Ave,Cleveland, OH 44195 USA Cleveland Clin Fdn NC10,9500 Euclid Ave Cleveland OH USA 44195
Citazione:
A.K. Majors e R.E. Pyeritz, "A deficiency of cysteine impairs fibrillin-1 deposition: Implications for the pathogenesis of cystathionine beta-synthase deficiency", MOL GEN MET, 70(4), 2000, pp. 252-260

Abstract

Cystathionine beta -synthase (CBS) deficiency is an inborn error of amino acid metabolism that has pleiotropic manifestations and is commonly called "homocystinuria. " The features include skeletal, ocular, and vascular defects, some of which are reminiscent of those found in Marfan syndrome (MFS). Because of the spectrum of clinical effects, the pathogenesis of homocystinuria has long been thought to involve the extracellular matrix (ECM), and the condition has been classified as a heritable disorder of connective tissue. Because of the superficial similarities with MFS, we and others (Pyeritz, in McKusicks Heritable Disorders of Connective Tissue, St. Louis, Mosby-Year Book Inc., 5th ed., pp 137-178, 1993; Pyeritz, in Principles and Practice of Medical Genetics, New York, Churchill Livingstone, 3rd ed., pp 1027-1066, 1997; Mudd, Levy, and Skovby, in The Metabolic and Molecular Bases ofinherited Disease, New York, McGraw-Hill Publishing Co., 7th ed., pp 1279-1327, 1995) have speculated how CBS deficiency might affect fibrillin-1, the protein altered in MFS. For example, the altered plasma concentrations ofhomocysteine and/or cysteine in patients with CBS deficiency may hinder fibrillin-1 synthesis, deposition, or both. When arterial smooth muscle cellswere cultured under conditions of cysteine deficiency, fibrillin-1 deposition into the ECM was greatly diminished as revealed by immunocytochemistry. Excessive homocysteine, in contrast, had little, if any, effect on fibrillin-1 deposition. When cysteine concentrations were returned to normal, the smooth muscle cells began to accumulate a matrix rich in fibrillin-1. Type I collagen, the major matrix component synthesized by these smooth muscle cells, was not reduced by low cysteine concentrations nor high homocysteine concentrations. These results demonstrate that a deficiency of cysteine andsubsequent inhibition of fibrillin-1 accumulation in CBS deficient patients may be at least partly responsible for their phenotype, and suggest that maintenance of normal plasma cyst(e)ine levels may be an important therapeutic goal. (C) 2000 Academic Press.

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Documento generato il 30/11/20 alle ore 08:54:51