Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schachtrup, C; Emmler, T; Bleck, B; Sandqvist, A; Spener, F.
Functional analysis of peroxisome-proliferator-responsive element motifs in genes of fatty acid-binding proteins.
Biochem J. 2004; 382(Pt 1):239-245
Doi: 10.1042/BJ20031340
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- Führende Autor*innen der Med Uni Graz
- Spener Friedrich
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- Abstract:
- Retinoic acids and long-chain fatty acids are lipophilic agonists of nuclear receptors such as RXRs (retinoic X receptors) and PPARs (peroxisome-proliferator-activated receptors) respectively. These agonists are also ligands of intracellular lipid-binding proteins, which include FABPs (fatty acid-binding proteins). We reported previously that L (liver-type)-FABP targets fatty acids to the nucleus of hepatocytes and affects PPARalpha activation, which binds together with an RXR subtype to a PPRE (peroxisome-proliferator-responsive element). In the present study, we first determined the optimal combination of murine PPAR/RXR subtypes for binding to known murine FABP-PPREs and to those found by computer search and then tested their in vitro functionality. We show that all PPARs bind to L-FABP-PPRE, PPARalpha, PPARgamma1 and PPARgamma2 to A (adipocyte-type)-FABP-PPRE. All PPAR/RXR heterodimers transactivate L-FABP-PPRE, best are combinations of PPARalpha with RXRalpha or RXRgamma. In contrast, PPARalpha heterodimers do not transactivate A-FABP-PPRE, best combinations are of PPARgamma1 with RXRalpha and RXRgamma, and of PPARgamma2 with all RXR subtypes. We found that the predicted E (epidermal-type)- and H (heart-type)-FABP-PPREs are not activated by any PPAR/RXR combination without or with the PPAR pan-agonist bezafibrate. In the same way, C2C12 myoblasts transfected with promoter fragments of E-FABP and H-FABP genes containing putative PPREs are also not activated through stimulation of PPARs with bezafibrate applied to the cells. These results demonstrate that only PPREs of L- and A-FABP promoters are functional, and that binding of PPAR/RXR heterodimers to a PPRE in vitro does not necessarily predict transactivation.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Base Composition - physiology
- Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology
- Carrier Proteins - genetics Carrier Proteins - physiology
- Cell Line, Tumor -
- DNA - genetics DNA - metabolism
- Dimerization -
- Fatty Acid-Binding Proteins -
- Gene Expression Regulation - physiology
- Genes - physiology
- Genes, Reporter - genetics
- Humans -
- Liver Neoplasms - genetics Liver Neoplasms - pathology
- Mice -
- Myoblasts - chemistry Myoblasts - metabolism
- Peroxisome Proliferator-Activated Receptors - metabolism Peroxisome Proliferator-Activated Receptors - physiology
- Peroxisome Proliferators - metabolism
- Promoter Regions, Genetic - physiology
- Response Elements - physiology
- Retinoid X Receptors - metabolism Retinoid X Receptors - physiology
- Transcriptional Activation - genetics Transcriptional Activation - physiology
- Find related publications in this database (Keywords)
- Dynabead streptavidin solid-phase method
- fatty acid-binding protein
- peroxisome-proliferator-activated receptor
- peroxisome-proliferator-response element
- reporter gene assay