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

Andrea Galli, Mark Stewart, Ryan Dorris, David Crabb

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24 Citations (Scopus)

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 PPARα 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 (RXRα) than CV-1 cells; cotransfection of CV-1 cells with PPARα plus RXRα 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 PPARα, such as hepatocytes and kidney cells, these factors are constitutively active; (2) activators of PPARα 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 PPARα.

Original languageEnglish
Pages (from-to)288-294
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume354
Issue number2
DOIs
StatePublished - Jun 15 1998

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Retinoid X Receptors
Peroxisome Proliferator-Activated Receptors
Hepatocellular Carcinoma
Genes
Ligands
Clofibrate
Liver
Lipids
Cells
Chromatographic analysis
Peroxisome Proliferators
Kidney
Reporter Genes
Plasmids
Binding Sites
1,2-diamino-1,2-N,N'-carbonyl-1,2-dideoxyglucose hydrate
Tissue
Cell Extracts
Chromatography
Hepatocytes

Keywords

  • Clofibrate
  • Lipid
  • Liver
  • Retinoid
  • Tissue specificity

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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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 PPARα 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 (RXRα) than CV-1 cells; cotransfection of CV-1 cells with PPARα plus RXRα 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 PPARα, such as hepatocytes and kidney cells, these factors are constitutively active; (2) activators of PPARα 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 PPARα.",
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T1 - High-level expression of RXRα and the presence of endogenous ligands contribute to expression of a peroxisome proliferator-activated receptor- responsive gene in hepatoma cells

AU - Galli, Andrea

AU - Stewart, Mark

AU - Dorris, Ryan

AU - Crabb, David

PY - 1998/6/15

Y1 - 1998/6/15

N2 - 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 PPARα 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 (RXRα) than CV-1 cells; cotransfection of CV-1 cells with PPARα plus RXRα 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 PPARα, such as hepatocytes and kidney cells, these factors are constitutively active; (2) activators of PPARα 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 PPARα.

AB - 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 PPARα 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 (RXRα) than CV-1 cells; cotransfection of CV-1 cells with PPARα plus RXRα 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 PPARα, such as hepatocytes and kidney cells, these factors are constitutively active; (2) activators of PPARα 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 PPARα.

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