Sterol regulatory element-binding proteins induce an entire pathway of cholesterol synthesis.

Sakakura, Y; Shimano, H; Sone, H; Takahashi, A; Inoue, N; Toyoshima, H; Suzuki, S; Yamada, N; Inoue, K

Sakakura, Y; Shimano, H; Sone, H; Takahashi, A; Inoue, N; Toyoshima, H; Suzuki, S; Yamada, N; Inoue, K.

Afiliación

Sakakura Y; Division of Metabolism and Endocrinology, Department of Internal Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukubashi, Ibaraki 305, Japan.

Biochem Biophys Res Commun ; 286(1): 176-83, 2001 Aug 10.

Article en En | MEDLINE | ID: mdl-11485325

RESUMEN

To evaluate the effects of sterol regulatory element-binding proteins (SREBPs) on the expression of the individual enzymes in the cholesterol synthetic pathway, we examined expression of these genes in the livers from wild-type and transgenic mice overexpressing nuclear SREBP-1a or -2. As estimated by a Northern blot analysis, overexpression of nuclear SREBP-1a or -2 caused marked increases in mRNA levels of the whole battery of cholesterogenic genes. This SREBP activation covers not only rate-limiting enzymes such as HMG CoA synthase and reductase that have been well established as SREBP targets, but also all the enzyme genes in the cholesterol synthetic pathway tested here. The activated genes include mevalonate kinase, mevalonate pyrophosphate decarboxylase, isopentenyl phosphate isomerase, geranylgeranyl pyrophosphate synthase, farnesyl pyrophosphate synthase, squalene synthase, squalene epoxidase, lanosterol synthase, lanosterol demethylase, and 7-dehydro-cholesterol reductase. These results demonstrate that SREBPs activate every step of cholesterol synthetic pathway, contributing to an efficient cholesterol synthesis.

Asunto(s)

Proteínas Potenciadoras de Unión a CCAAT/metabolismo; Colesterol/biosíntesis; Proteínas de Unión al ADN/metabolismo; Factores de Transcripción/metabolismo; Animales; Secuencia de Bases; Proteínas Potenciadoras de Unión a CCAAT/genética; Cartilla de ADN; Proteínas de Unión al ADN/genética; Difosfatos/metabolismo; Regulación Enzimológica de la Expresión Génica; Ratones; Ratones Transgénicos; Proteína 1 de Unión a los Elementos Reguladores de Esteroles; Proteína 2 de Unión a Elementos Reguladores de Esteroles; Factores de Transcripción/genética

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Colesterol / Proteínas Potenciadoras de Unión a CCAAT / Proteínas de Unión al ADN Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2001 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos

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