Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Oberkofler, H; Schraml, E; Krempler, F; Patsch, W.
Restoration of sterol-regulatory-element-binding protein-1c gene expression in HepG2 cells by peroxisome-proliferator-activated receptor-gamma co-activator-1alpha.
Biochem J. 2004; 381(Pt 2): 357-363.
Doi: 10.1042/BJ20040173
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- Co-Autor*innen der Med Uni Graz
- Schraml Elisabeth
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- Abstract:
- The expression of SREBP-1 (sterol-regulatory-element-binding protein-1) isoforms differs between tissues and cultured cell lines in that SREBP-1a is the major isoform in established cell lines, whereas SREBP-1c predominates in liver and most other human tissues. SREBP-1c is transcriptionally less active than SREBP-1a, but is a main mediator of hepatic insulin action and is selectively up-regulated by LXR (liver X receptor) agonists. LXR-mediated transactivation is co-activated by PGC-1alpha (peroxisome-proliferator-activated receptor-gamma co-activator-1alpha), which displays deficient expression in skeletal-muscle-derived cell lines. In the present paper, we show that PGC-1alpha expression is also deficient in HepG2 cells and in a human brown adipocyte cell line (PAZ6). In transient transfection studies, PGC-1alpha selectively amplified the LXR-mediated transcription from the human SREBP-1c promoter in HepG2 and PAZ6 cells via two LXR-response elements with extensive similarity to the respective murine sequence. Mutational analysis showed that the human LXR-response element-1 (hLXRE-1) was essential for co-activation of LXR-mediated SREBP-1c gene transcription by PGC-1alpha. Ectopic overexpression of PGC-1alpha in HepG2 cells enhanced basal SREBP-1c and, to a lesser extent, -1a mRNA expression, but only SREBP-1c expression was augmented further in an LXR/RXR (retinoic X receptor)-dependent fashion, thereby inducing mRNA abundance levels of SREBP-1c target genes, fatty acid synthase and acetyl-CoA carboxylase. These results indicate that PGC-1alpha contributes to the regulation of SREBP-1 gene expression, and can restore the SREBP-1 isoform expression pattern of HepG2 cells to that of human liver.
- Find related publications in this database (using NLM MeSH Indexing)
- Adipose Tissue - chemistry
- Adult - chemistry
- CCAAT-Enhancer-Binding Proteins - genetics
- Carcinoma, Hepatocellular - genetics
- Cell Line - genetics
- Cell Line, Tumor - genetics
- DNA-Binding Proteins - genetics
- Gene Expression Regulation, Neoplastic - genetics
- Heat-Shock Proteins - physiology
- Humans - physiology
- Kidney - chemistry
- Liver - chemistry
- Liver Neoplasms - genetics
- Male - genetics
- Middle Aged - genetics
- Rectus Abdominis - chemistry
- Sterol Regulatory Element Binding Protein 1 - chemistry
- Transcription Factors - genetics
- Find related publications in this database (Keywords)
- co-activator
- gene expression
- liver X receptor (LXR)
- peroxisome-proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1 alpha)
- sterol-regulatory-element-binding protein (SREBP)