Peroxisome proliferator-activated receptors isoforms

Wilkinson, A., Monteith, G., Shaw, P., Lin, C., Gidley, M., and Roberts-Thomson, S. 2008. Effects of the mango components mangiferin and quercetin and the putativemangiferimnetabo-lite norathyriol on the transactivation of peroxisome proliferator-activated receptor isoforms. J Journal of Agricultural and Food Chemistry, 56 (9), 3037-3042. 

In addition to PXR, the expression of UGT1A1 and several other UGT isoforms have also been reported to be regulated by several other nuclear receptors, including constitutive androstane receptor (CAR) [25,27,28] and peroxisome proliferator activated receptor a (PPARa) [29,30],... 

Lee SST, Pineau T, Drago J, et al. 1995. Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 15(6) 3012-3022. 

Zhu, Y., Qi, C., Korenberg, J. R., Chen, X. N., Noya, D., Rao, M. S., and Reddy, J. K. (1995). Structural Organization of Mouse Peroxisome Proliferator-Activated Receptor Gamma (mPPARy) Gene Alternative Promoter Use and Different Splicing Yield Two mPPARy Isoforms. Proc. Natl. Acad. Sci. U.S.A. 92, 7921-7925. 

Sugden MC, Bulmer K, Augustine D, and Holness MJ (2001a) Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha implications for glucose-stimulated insulin secretion. Diabetes 50, 2729-36. 

Costet, P., Legendre, C., More, J., Edgar, A., Galtier, P., and Pineau, T. Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dysli-pidemia with sexually dimorphic obesity and steatosis. J Biol Chem 273 (1998) 29577-29585. 

PPARs belong to a family of nuclear transcription factors that heterodimerize with retinoid X receptors (RXR) and function in a ligand-dependent manner [5]. They can activate transcription through binding peroxisome proliferator activated receptor response elements (direct repeat of AGGTCA spaced by one nucleotide). To date, three different PPAR isoforms a, 5/p, and y (and splice variants) have been identified that are encoded by separate genes. The tissue-specific expression pattern of these transcription factors is indicative of their function in those tissues [6]. 

The realization that the gene for PGHS-2 is an immediate early gene associated with cell replication and differentiation suggests that prostanoids synthesized via PGHS-2 may have nuclear effects. As noted above there have been several reports indicating that prostanoid derivatives can activate some isoforms of peroxisomal proliferator activated receptors (PPARs). There is evidence that PGIj can be involved in PPARS-mediated responses such as decidualization and apoptosis (PA. Scherle, 2000). 

M. U. Krishna, J.R. Faick et al. (2002). The CYP 4A isoforms hydroxylate epoxyeicosatrienoic acids to form high affinity peroxisome proliferator-activated receptor ligands. J. Biol. Chem. 277,35105-35112. 

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily. The three PPAR isoforms (a, p/8, and y) are known to occur in mammalian tissues. In response to specific agonists, these receptors form dimers and translocate to the nucleus, where they act as agonist-dependent transcription factors and regulate gene... 

CLA has also been shown to be a good ligand of nuclear receptors called peroxisome proliferator activated receptors (PPAR) (45). CLA is specifically active on two PPAR isoforms, a and y. The isoform a is found mainly in liver and functions as a transcription factor for many enzymes involved in fatty acid oxidation and particularly, peroxisomal 3-oxidation. We recently detected peroxisomal 3-oxidation products of CLA and metabolites in rat tissues and in humans (unpublished data). This finding would prompt the question whether CLA, as a good substrate for peroxisomal 3-oxidation, has any effect on peroxisomal P-oxidation. Indeed, it has been reported that induction of several key enzymes of peroxisomal P-oxidation was through the activation of PPARa by CLA (45). 

Sundvold, H., Brzozowska, A., and Lien, S. (1997) Characterisation of Bovine Peroxisome Proliferator-Activated Receptors yl and y2 Genetic Mapping and Differential Expression of the Two Isoforms, Biochem. Biophys. Res. Commun. 239, 857-861. 

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