Reduction in cholesterol synthesis in response to serum starvation in lymphoblasts of a patient with Barth syndrome.
Biochem Cell Biol
; 88(4): 595-602, 2010 Aug.
Article
em En
| MEDLINE
| ID: mdl-20651830
ABSTRACT
Barth syndrome is a rare X-linked disease in which mild hypocholesterolemia is observed in some patients. We investigated cholesterol biosynthesis in lymphoblasts from a normal and age-matched Barth syndrome patient. Control and Barth syndrome (DeltaTAZ1) lymphoblasts were incubated in the presence or absence of serum to induce cholesterol synthesis and hydroxymethylglutaryl-coenzyme A reductase activity and expression, and cholesterol biosynthesis from radioactive precursors was determined. Cholesterol biosynthesis from [2-14C]pyruvate was stimulated 2-fold in control cells, but was unchanged in DeltaTAZ1 lymphoblasts, and from [1-14C]acetate was stimulated 77% in control but only 26% in DeltaTAZ1 lymphoblasts upon serum removal, indicating a lower ability of DeltaTAZ1 cells to upregulate cholesterol biosynthesis. The reason was an inability to increase hydroxymethylglutaryl-coenzyme A reductase activity, which was already near maximum in DeltaTAZ1 lymphoblasts, in response to serum removal, compared with control cells. The reduced ability to increase hydroxymethylglutaryl-coenzyme A reductase enzyme activity in DeltaTAZ1 lymphoblasts was due to a decrease in hydroxymethylglutaryl-coenzyme A reductase messenger RNA. Although total cholesterol levels are similar under standard culture conditions, DeltaTAZ1 lymphoblasts have a diminished capacity to respond to increased demand for cholesterol biosynthesis because of an already elevated level of synthesis under standard culture conditions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
/
Colesterol
/
Meios de Cultura Livres de Soro
/
Síndrome de Barth
Limite:
Humans
Idioma:
En
Revista:
Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Canadá