The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.
J Clin Invest
; 104(8): R25-31, 1999 Oct.
Article
em En
| MEDLINE
| ID: mdl-10525055
ABSTRACT
The ABC1 transporter was identified as the defect in Tangier disease by a combined strategy of gene expression microarray analysis, genetic mapping, and biochemical studies. Patients with Tangier disease have a defect in cellular cholesterol removal, which results in near zero plasma levels of HDL and in massive tissue deposition of cholesteryl esters. Blocking the expression or activity of ABC1 reduces apolipoprotein-mediated lipid efflux from cultured cells, and increasing expression of ABC1 enhances it. ABC1 expression is induced by cholesterol loading and cAMP treatment and is reduced upon subsequent cholesterol removal by apolipoproteins. The protein is incorporated into the plasma membrane in proportion to its level of expression. Different mutations were detected in the ABC1 gene of 3 unrelated patients. Thus, ABC1 has the properties of a key protein in the cellular lipid removal pathway, as emphasized by the consequences of its defect in patients with Tangier disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas
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Doença de Tangier
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Glicoproteínas
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Transportadores de Cassetes de Ligação de ATP
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Metabolismo dos Lipídeos
Limite:
Adolescent
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Animals
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Humans
/
Male
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article