Peroxisome proliferator-activated receptor transcriptional regulation

Tan, N. S., N. S. Shaw, N. Vinckenbosch, et al. 2002. Selective Cooperation Between Fatty Acid Binding Proteins and Peroxisome Proliferator-Activated Receptors in Regulating Transcription. Mol Cell Biol 22, no 14 5114-27. 

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 (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARa is implicated in the regulation of lipid metabolism, lipoprotein synthesis, and inflammatory response in liver and other tissues. 

TF transcription factor, R receptor, Fur ferric uptake regulation protein, NF-kB nuclear factor-kB, AP-1 activator protein-1, Egr-1 early growth response-1, VDR la,25-dihydroxy-vitamin D3 receptor, RXR retinoid X receptor, PPARy peroxisome proliferator-activated receptor y NFAT nuclear factor of activated T-cells, HSF heat shock factor, p53 tumor suppressor p53, HIF-1 hypoxia inducible factor-1. ... 

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.

Another forefront technique to improve the function of the stratum corneum and enhance barrier repair in dry skin is the use of epidermal differentiation. A number of hormone receptors for epidermal differentiation have been identified. This family of receptors includes retinoic acid receptors, the steroid receptors, the thyroid receptors, the Vitamin D receptors, the peroxisome proliferator-activated receptors, the farnesol-activated receptors, and the liver-activated receptors. It is reported that these transcription factors bind their respective ligands and regulate many of the aspects of cellular proliferation and differentiation. Examples of ligands for the last three transcription factors are fatty acids for the peroxisome proliferator-activated receptor, famesol for the farnesol-activated receptor, and hydroxylated cholesterol derivatives for the liver-activated receptor. The stimulation of epidermal differentiation stimulated the synthesis of involucrin, filaggrin, and the enzymes of the ceramide synthesis pathway (74). 

Statins, used predominantly in the treatment of hypercholesterolemia, act by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which regulates the synthesis of cholesterol. Statins are also agonists of peroxisome proliferator activated receptors (PPARs), which are part of the nuclear receptor superfamily and when activated, can suppress transcription of pro-inflammatory genes (Chinetti et al., 2000). In vitro and in vivo studies have shown that a decrease in serum cholesterol inhibits the production of beta amyloid and plaque (Simons et al., 1998 Fassbender et al.,... 

M. E. Young, S. Patil, J. Ying, C. Depre, H. S. Ahuja, G. L. Shipley, S. M. Stepkowski, P. J. Davies and H. Taegtmeyer, Uncoupling protein 3 transcription is regulated by peroxisome proliferator-activated receptor (alpha) in the adult rodent heart, FASEB J15, 833-845 (2001). 

Peroxisome proliferator-activated receptors (PPARs) comprise another subfamily of nuclear receptors whose members regulate the transcription of genes controlling fatty acid oxidation, including CYP4A (lauric acid hydroxylases). PPAR a, /3 (also known... 

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