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Phosphorylation of sterol regulatory element-binding protein (SREBP)-1a links growth hormone action to lipid metabolism in hepatocytes.

Abstract：

OBJECTIVE:Increased lipid accumulation in cells and tissues is a key phenomenon in the development of obesity, insulin resistance, and atherosclerosis. In the regulation of lipid content of cells and tissues the SREBPs play a dominant role as transcription factors. METHODS:Since growth hormone (GH) affects lipid metabolism and function of fat as well as liver cells, we have investigated the role of SREBP-1a, SREBP-1c and SREBP-2 in the gene regulatory action of GH in the human liver cell line HepG2 and primary mouse hepatocytes. RESULTS:These experiments showed that SREBP-1a couples the stimulatory effect of GH on cholesterol regulated genes, e.g. LDL receptor gene, via sterol sensitive binding cis-element (sre-1). This effect was not depending on RNA expression, but related to phosphorylation of SREBP-1a protein. The result was supported by experiments with the mutant variant SREBP-1a S117A, which is not phosphorylated by Erk-MAP kinases. To analyse a possible role of GH-induced SREBP-1a phosphorylation in cellular physiology we investigated an expression profile of genes coding for central players in lipid transport or lipid metabolism as well as for transcription factors by real time PCR in primary mouse hepatocytes and human hepatoma cell line stably overexpressing the mature form of SREBP-1a or mutated form. CONCLUSION:These experiments emphasize the role SREBP-1a and its phosphorylation for gene regulatory effects of GH.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Kotzka J,Knebel B,Avci H,Jacob S,Nitzgen U,Jockenhovel F,Heeren J,Haas J,Muller-Wieland D

doi

10.1016/j.atherosclerosis.2010.08.046

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

156-65

issue

1

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(10)00687-8

journal_volume

213

pub_type

杂志文章

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