Assay for ppar ligand dependent gene modulation

The peroxisome proliferator activated receptor alpha (PPARalpha) plays a key role in mediating fatty acid metabolism by regulating expression of genes involved in fatty acid oxidation. A limitation of existing human cell models for testing PPARalpha ligands is the inability to detect PPAR responsive...

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Hauptverfasser:	PHILLIP LIU, RANJAN MUKHERJEE, TIMOTHY C. BURN, REID M. HUBER, PETER R. YOUNG
Format:	Patent
Sprache:	eng
Schlagworte:	BEER BIOCHEMISTRY CHEMISTRY COMPOSITIONS OR TEST PAPERS THEREFOR CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES ENZYMOLOGY MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS METALLURGY MICROBIOLOGY MUTATION OR GENETIC ENGINEERING PROCESSES OF PREPARING SUCH COMPOSITIONS SPIRITS VINEGAR WINE
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Beschreibung
Zusammenfassung:	The peroxisome proliferator activated receptor alpha (PPARalpha) plays a key role in mediating fatty acid metabolism by regulating expression of genes involved in fatty acid oxidation. A limitation of existing human cell models for testing PPARalpha ligands is the inability to detect PPAR responsive genes with endogenous levels of PPARalpha protein. The HK-2 cell line derived from human proximal tubules showed induction of several genes, including pyruvate dehydrogenase kinase 4 (PDK-4) and adipocyte differentiation related factor (ADRP) by PPARalpha ligands. Induction of PDK-4 by PPARalpha agonists in the HK-2 cell model closely correlates with its induction in vivo and thus represents a marker for PPARalpha agonist action. HK2 cells also exemplify the first model of a human cell line in which PPARalpha ligand dependent gene induction can be detected with endogenous levels of receptor.