High-level expression of RXRalpha and the presence of endogenous ligands contribute to expression of a peroxisome proliferator-activated receptor-responsive gene in hepatoma cells.

Abstract

Genes containing peroxisome proliferator-activated receptor (PPAR) binding sites are both inducible by peroxisome proliferators and expressed in a tissue-specific fashion. A PPAR-responsive reporter gene cotransfected with a PPARalpha expression vector was highly expressed in H4IIEC3 hepatoma cells. Addition of clofibrate resulted in a modest further induction of the reporter gene. In CV-1 cells, high expression of the reporter required the addition of clofibrate. H4IIEC3 cells had higher levels of retinoid X receptor (RXRalpha) than CV-1 cells; cotransfection of CV-1 cells with PPARalpha plus RXRalpha expression plasmids abolished the cell line difference in basal and clofibrate-stimulated expression of the reporter. Lipid extracts of hepatoma cells or of liver or kidney stimulated expression of the reporter; extracts of CV-1 cells were far less effective. Chromatographic analysis of these extracts revealed high levels of three fractions of lipid in liver and H4IIEC3 cells that were lower in CV-1 cells. We conclude that (1) in cells expressing high levels of both RXRs and PPARalpha, such as hepatocytes and kidney cells, these factors are constitutively active; (2) activators of PPARalpha may increase its ability to form heterodimers with RXRs when the latter are limiting; and (3) hepatoma cells, liver, and kidney contain lipid-extractable compounds capable of activating PPARalpha.

• Authors: A Galli, M Stewart, R Dorris, D Crabb
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 354 Issue 2 Pg. 288-94 (Jun 15 1998) ISSN: 0003-9861 [Print] United States
• PMID: 9637738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 1998 Academic Press.

Chemical References

• Receptors, Cytoplasmic and Nuclear
• Receptors, Retinoic Acid
• Retinoid X Receptors
• Transcription Factors
• Tretinoin
• Luciferases
• Clofibrate

Topics

• Carcinoma, Hepatocellular (genetics)
• Clofibrate (pharmacology)
• Gene Expression Regulation
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• Liver (metabolism)
• Luciferases (genetics)
• Receptors, Cytoplasmic and Nuclear (physiology)
• Receptors, Retinoic Acid (biosynthesis)
• Retinoid X Receptors
• Transcription Factors (biosynthesis, physiology)
• Tretinoin (pharmacology)
• Tumor Cells, Cultured