Peroxisome proliferator activated receptor-y

The thiazolidinediones have also been reported to act as inhibitors of the respiratory chain at high concentrations, and this appears to account for their ability to activate AMGPK in cultured cells. However, the primary target of the thiazolidinediones appears to be the peroxisome proliferator-activated receptor-y ( PPAR-y), a member of the nuclear receptor superfamily expressed in adipocytes. One of the major effects of stimulation of PPAR-y in adipocytes is the release ofthe... 

Thiazolidinediones (PPARy-agonists) Thiazolidine-diones ( pioglitazone, rosiglitazone) lower blood glucose levels in animal models of insulin resistance and also in insulin resistant patients. They are agonists of the peroxisome proliferator-activated receptor y (PPARy). Because they enhance the effect of insulin and reduce serum insulin levels in insulin resistant patients, thiazolidinediones are usually referred to as insulin sensitizers . 

Finally, it has to be mentioned that LPA also has an intracellular target site, which is the nuclear transcription factor, peroxisome proliferator-activated receptor-y (PPARy). LPA competes for thiazolidinedione binding and activates PPARy-dependent gene transcription. Thereby, LPA induced neointima formation in a rat carotid artery model. 

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. ... 

Han, K. L., Jung, M. H., Sohn, J. H., and Hwang, J.-K. (2006). Ginsenoside 20(S)-protopanax-atriol (PPT) activates peroxisome proliferator-activated receptor y (PPARy) in 3T3-L1 adipocytes. Biol. Pharm. Bull. 29,110-113. 

Schupp, M., Clemenz, M., Gineste, R., Witt, H., Janke, J., Helleboid, S., Hennuer, N., Ruiz, P., Unger, T., Staels, B., and Kintscher, U. (2005). Molecular characterization of new selective peroxisome proliferator-activated receptor y modulators with angiotensin receptor blocking activity. Diabetes 54, 3442-3452. 

Thiazolidinediones are the newer agents that favourably influence insulin sensitivity and possibly also pancreatic fS-cell function. The biological response of thiazolidinediones is mediated by binding to the nuclear peroxisome proliferator-activated receptor-y (PPAR)... 

The farnesoid X receptor is a member of the class of nuclear hormone receptors, which have key roles in development and homeostasis, as well as in many diseases like obesity, diabetes and cancer. The farnesoid X receptor shows structural similarity to the estrogen receptor (ER ), which mediates a broad spectrum of physiological functions such as regulation of reproduction, modulation of bone density, cholesterol transport and breast cancer. The farnesoid X receptor also shows similarity with the peroxisome proliferation-activated receptor y (PPARy), which is involved in fat metabolism, inflammatory and immune responses. The estrogen receptor (ER ), the peroxisome proliferation-activated receptor y (PPARy) and the farnesoid X receptor (FXR) can be clustered in a... 

Sharma AM, Staels B. Review peroxisome proliferator-activated receptor y and adipose tissue - understanding obesity-related changes in regulation of lipid and glucose metabolism. J Clin Endocrinol Metab 2007 92 386-95. 

Liang, Y.C. et ah. Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-y by flavonoids in mouse macrophages, FEBS Lett., 496, 12, 2001. 

Yamazaki R., Kusunoki N., Matsuzaki T., Hashimoto S., and Kawai S. (2002). Nonsteroidal antiinflammatory drugs induce apoptosis in association with activation of peroxisome proliferator-activated receptor y in rheumatoid synovial cells. J. Pharmacol. Exp. Ther. 302 18-25. 

Berger, J., Bailey, P., Biswas, C., Cullinan, C. A., Doebber, T. W., Hayes, N. S., Saper-stein, R., Smith, R. G., and Leibowitz, M. D. (1996). Thiazolidinediones Produce a Conformational Change in Peroxisomal Proliferator-Activated Receptor-y Binding and Activation Correlate with Antidiabetic Actions in db/db Mice. Endocrinology 137, 4189-4195. 

Kruszynska, Y. T., Mukheijee, R.,Jow, L., Dana, S., Paterniti,J. R., and 01efsky,J. M. (1998). Skeletal Muscle Peroxisome Proliferator-Activated Receptor-y Expression in Obesity and Non-Insulin-Dependent Diabetes Mellitus. J. Clin. Invest. 101, 543-548. 

Meirhaeghe, A., Fajas, L., Helbecque, N., Cottel, D., Lebel, R, Dallongeville, J., Deeb, S., Auwerx, J., and Amouyel, R (1998). A Genetic Polymorphism of the Peroxisome Proliferator-Activated Receptor y Gene Influences Plasma Leptin Levels in Obese Humans. Hum. Mol. Genet. 7, 435-440. 

Yen, C.-J., Beamer, B. A., Negri, C., Silver, K., Brown, K. A., Yarnell, D. P., Burns, D. K., Roth, J., and Shuldiner, A. R. (1997). Molecular Scanning of the Human Peroxisome Proliferator Activated Receptor y Gene in Diabetic Caucasians Identification of a Prol2Ala PPARy2 Missense Mutation. Biochem. Biophys. Res. Commun. 241, 270-274. 

Buckingham, R. E., Al-Barazanji, K. A., Toseland, C. 1). N. el al. (1998). Peroxisome Proliferator-Activated Receptor-y Agonist, Rosiglitazone, Protects Against Nephropathy and Pancreatic Islet Abnormalities in Zucker Fatty Rrts. Diabetes 47, 1326-1334. 

Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A. et al. (1995). An Antidiabetic Thi-azolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-Activated Receptor y (PPARy). /. Biol. Chem. 270, 12953-12956. 

Burris TP, Pelton PD, Zhou L, et al. A novel method for analysis of nuclear receptor function at natural promoters peroxisome proliferator-activated receptor y agonist actions on a P2 gene expression detected using branched DNA messenger RNA quantitation. Mol Endocrinol 1999 13 410—417. 

---