Ligands peroxisome proliferator-activated receptor

A peroxisome proliferator-activated receptor (PPAR) binding site was identified in the murine FATP1 promoter. Several reports have shown a positive regulation of mouse FATPs by ligands that activate PPAR-a, PPAR-y, or PPAR-y/RXR heterodimers. 

Peraza MA, Burdick AD, Marin HE et al (2006) The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR). Toxicol Sci 90 269-295... 

Peroxisome Proliferator-Activated Receptors. Figure 3 Transcription of PPAR target genes. A schematic representation of the transcription of PPAR-regulated genes in the absence (a) and presence (b) of PPAR ligand. Abbreviations PPAR-RE, peroxisome proliferator-activated receptor-response element RNA Pol II, RNA polymerase II TATA-BP, TATA-binding protein. 

Peroxisome Proliferator-Activated Receptors. Table 4 Summary of the physiological actions of PPAR isotypes and their synthetic ligands... 

Brown, P. J., Smith-Oliver, T. A., Charifson, P. S., et al. (1997) Identification of peroxisome proliferator-activated receptor ligands from a biased chemical library. 

Although prostanoids can activate peroxisome proliferator-activated receptors (PPARs) if added in sufficient concentration in vitro, it remains questionable whether these compounds attain concentrations sufficient to function as endogenous nuclear-receptor ligands in vivo. 

Diep, Q. N., Touyz, R. M., and Schiffrin, E. L. (2000). Docosahexaenoic acid, a peroxisome proliferator-activated receptors-a ligand induces apoptosis in vascular smooth muscle cells by stimulation of p38 mitogen-activated protein kinase. Hypertension 36, 851-855. 

Research has now established that the peroxisome proliferators act on a receptor, called the peroxisome proliferator-activated receptor (PPAR), discovered in 1990. There are now known to be three receptors PPARa, PPARS, and PPARy. These are parts of the nuclear hormone super family. The PPARs are ligand-dependent transcription factors, which have different functions and tissue locations. 

Proteins in a family of ligand-activated transcription factors, the peroxisome proliferator-activated receptors (PPARs), respond to changes in dietary lipid by... 

Cuzzocrea, S., Di Paloa, R., Mazzon, E., Genovese, T., Muia, C., Centorrino, T., and Caputi, A. P. (2004). Role of endogenous and exogenous ligands for the peroxisome proliferators activated receptors alpha (PPAR-alpha) in the development of inflammatory bowel disease in mice. Lab. Invest. 84, 1643-1654. 

Forman, B. M., Chen, J., and Evans, R. M. (1997). Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc. Natl. Acad. Sci. USA 94, 4312-4317. 

Konturek, P. C., Brzozowski, T., Kania, J., Konturek, S. J., Kwiecien, S., Pajdo, R., and Hahn, E. G. (2003). Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, accelerates gastric ulcer healing in rat. Eur.J. Pharmacol. 472, 213-220. 

Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A., Wilkison, W. O., Willson, T. M., and Kliewer, S. A. (1995). An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-Activated Receptor Gamma (PPAR Gamma). J. Biol. Chem. 270,12953-12956. 

Xin X, Yang, S., Kowalski, J., and Gerritsen, M. E. (1999). Peroxisome Proliferator-Activated Receptor Gamma Ligands Are Potent Inhibitors of Angiogenesis In Vitro and In Vivo./ Biol. Chem. 274, 9116-9121. 

LPL M-CSFR MHC MHC-II MMCP MMP NG2 PDGF PPAR RANK Sca-1 SM22 L lipoprotein monocyte - colony stimulation factor receptor myosin heavy chain MHC class II mouse mast cell protease metalloproteinase proteoglycan heparan-sulfate related to pericytes activity platelet-derived growth factor peroxisome proliferator-activated receptor gamma receptor activator of NF-kappa 3 stem cell antigen 1 smooth cell protein structurally related to calponin, both actin and tropomyosin ligands... 

Xu, H.E. etal. Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors, Proc. Natl Acad. Sci. USA, 24, 13919, 2001. 

Figure 29-6. Gene transcription is regulated by retinoic acid.Ah-Zrwm-retinoic acid and 9-cA-retinoic acid are ligands for retinoic acid receptors (RARs) and retinoid X receptors (RXRs), respectively. The RXRs can form heterodimers with RARs and with the thyroid hormone receptors (TRs), the vitamin D receptor (VDR), and the peroxisome proliferator-activated receptors (PPARs) and a number of other hormone- and nutrient-responsive transcription factors to moderate gene transcription. Because of the ability of RXR to form heterodimers with other nuclear receptors, vitamin A has abroad effect on many hormonally and nutrient-responsive genes.

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