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PPAR Ligands (ppar + ligand)

Distribution by Scientific Domains
Medical Sciences60%
Life Sciences40%

Selected Abstracts

Peroxisome Proliferator-Activated Receptors (PPAR) and the Mitochondrial Aldehyde Dehydrogenase (ALDH2) Promoter In Vitro and In Vivo

ALCOHOLISM, Issue 7 2001
David W. Crabb
Background : The aldehyde dehydrogenase 2 (ALDH2) promoter contains a nuclear receptor response element (NRRE) that represents an overlapping direct repeat-1 (DR-1) and -5 (DR-5) element. Because DR-1 elements are preferred binding sites for peroxisome proliferator-activated receptors (PPARs), we tested the hypothesis that PPARs regulate ALDH2 expression. Methods: We examined the ability of PPAR isoforms to bind to the ALDH2 NRRE in electrophoretic mobility shift assays, their ability to activate the transcription of promoter-reporter constructs containing this NRRE, the effect of PPAR ligands on ALDH2 expression in liver, and the role of the PPAR, on the expression of ALDH2 by using PPAR,-null mice. Results: In vitro translated PPARs bound the ALDH NRRE with high affinity. Mutation of the NRRE indicated that binding was mediated by the DR-1 element. Cotransfection of PPAR expression plasmids showed that PPAR, had no effect on expression of heterologous promoter constructs containing the NRRE. PPAR, slightly induced expression, whereas PPAR, repressed basal activity of the promoter and blocked induction by hepatocyte nuclear factor 4. Treatment of rats with the PPAR ligand clofibrate repressed expression of ALDH2 in rats fed either stock rodent chow or a low-protein diet. Consistent with the transfection data, expression of ALDH2 protein was not different in PPAR,-null mice. Treatment of the mice with the PPAR, agonist WY14643 slightly decreased the level of ALDH2 protein in both wild-type and PPAR,-null mice, suggesting that the effect of WY14643 was not mediated by the receptor. Conclusions: These data indicate that ALDH2 is not part of the battery of lipid metabolizing enzymes and proteins regulated by PPAR, [source]

Auraptene, a citrus fruit compound, regulates gene expression as a PPAR, agonist in HepG2 hepatocytes

BIOFACTORS, Issue 1 2008
Nobuyuki Takahashi
Abstract Citrus fruit compounds have various activities that improve pathological conditions in many tissues. In this study, we examined the effect of auraptene contained mainly in the peel of citrus on peroxisome proliferator-activated receptor-, (PPAR,) activation. To examine effects of auraptene on the PPAR, activation in hepatocytes, PPAR ligand assay system was developed using HepG2 hepatocytes, in which the endogenous PPAR, expression level is very low. In the PPAR ligand assay, the addition of auraptene showed significant effects on the transactivation of GAL4/PPAR, chimera proteins in a dose-dependent manner. Actually, treatment with auraptene induced the up-regulation of PPAR target genes, such as acyl-CoA oxidase (ACO), carnitine-palmitoyl transferase 1A (CPT1A) and acyl-CoA synthetase (ACS), in PPAR,-expressing HepG2 hepatocytes. The regulation of gene expression was dependent on PPAR, because mock-transfected HepG2 hepatocytes showed no regulation. The up-regulation of PPAR target gene expression by auraptene was sufficient to enhance oleic acid uptake into PPAR,-expressing HepG2 hepatocytes. These results indicate that auraptene acts as a PPAR, agonist in hepatocytes and that auraptene may improve lipid abnormality through PPAR, activation in the liver. [source]

Peroxisome proliferator-activated receptors (PPARs) in the control of bone metabolism

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2007
Costas Giaginis
Abstract Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that regulate the storage and catabolism of dietary fats. PPARs constitute molecular targets for the treatment of human metabolic disorders, and also play a crucial role in inflammatory-related disease and cancer. Recent evidence has revealed the presence of three different PPAR isotypes (,, ,/,, and ,) in different cells of the bone tissue, as well as the possible role of PPAR ligands in bone turnover. In the present review, the latest knowledge of the expression of PPARs in bone tissue and the diverse effects of PPAR ligands on bone metabolism is summarized. PPARs, especially of the , isotype, could be targets for the treatment of diverse bone diseases such as osteoporosis and osteopenia related to either diabetes or aging. [source]

PPAR gamma activators induce differentiation of B12 oligodendrocyte-like cells and rat spinal cord oligodendrocytes

JOURNAL OF NEUROCHEMISTRY, Issue 2002
A. D. Roth
The regulation of CNS lipid metabolism by nuclear receptors and their relation to cell differentiation remains undetermined. Since myelinating oligodendrocytes are the major lipid-synthesizing cells in the CNS, we characterized the effect of PPAR activation in a CNS derived cell line that expresses oligodendrocyte markers and compared these effects with oligodendrocyte primary cultures (90,95% pure). The rat glioma derived B12 cell line express the three major PPAR isoforms (PPAR ,, , and ,) and present a large number of peroxisomes, indicating an important lipid metabolism. Treatment with ciprofibrate, a general PPAR activator and clinical hypolipidemic, induces proliferation arrest, process extension and a moderate rise in the expression of acyl-CoA oxidase, a specific marker of peroxisomal proliferation. Cell growth arrest by ciprofibrate is enhanced 100-fold by low concentrations of retinoic acid (0.01 ,m), suggesting the involvement of the PPAR-retinoid acid receptor heterodimers. Since ciprofibrate possibly acts by modifying the concentration of endogenous PPAR ligands, we traced its effects to PPAR, by using isoform specific ligands: Troglitazone and 15-deoxy-prostaglandin J2, both of which induce growth arrest and process extension in B12 cells. These effects were corroborated on rat spinal cord derived oligodendrocytes primary cultures, where a significant rise in the number of mature oligodendrocytes is observed in response to PPAR, activators. These results show that PPAR,, a master gene in the differentiation of adipose tissue could be involved in the lipid metabolism of maturing oligodendrocytes. [source]

Peroxisome Proliferator-Activated Receptors (PPAR) and the Mitochondrial Aldehyde Dehydrogenase (ALDH2) Promoter In Vitro and In Vivo

ALCOHOLISM, Issue 7 2001
David W. Crabb
Background : The aldehyde dehydrogenase 2 (ALDH2) promoter contains a nuclear receptor response element (NRRE) that represents an overlapping direct repeat-1 (DR-1) and -5 (DR-5) element. Because DR-1 elements are preferred binding sites for peroxisome proliferator-activated receptors (PPARs), we tested the hypothesis that PPARs regulate ALDH2 expression. Methods: We examined the ability of PPAR isoforms to bind to the ALDH2 NRRE in electrophoretic mobility shift assays, their ability to activate the transcription of promoter-reporter constructs containing this NRRE, the effect of PPAR ligands on ALDH2 expression in liver, and the role of the PPAR, on the expression of ALDH2 by using PPAR,-null mice. Results: In vitro translated PPARs bound the ALDH NRRE with high affinity. Mutation of the NRRE indicated that binding was mediated by the DR-1 element. Cotransfection of PPAR expression plasmids showed that PPAR, had no effect on expression of heterologous promoter constructs containing the NRRE. PPAR, slightly induced expression, whereas PPAR, repressed basal activity of the promoter and blocked induction by hepatocyte nuclear factor 4. Treatment of rats with the PPAR ligand clofibrate repressed expression of ALDH2 in rats fed either stock rodent chow or a low-protein diet. Consistent with the transfection data, expression of ALDH2 protein was not different in PPAR,-null mice. Treatment of the mice with the PPAR, agonist WY14643 slightly decreased the level of ALDH2 protein in both wild-type and PPAR,-null mice, suggesting that the effect of WY14643 was not mediated by the receptor. Conclusions: These data indicate that ALDH2 is not part of the battery of lipid metabolizing enzymes and proteins regulated by PPAR, [source]