Peroxisome proliferator-activated receptors functions

Peroxisome Proliferator-Activated Receptors. Figure 1 Common structural and functional features of nuclear receptor transcription factors. Consistent with other members of the nuclear receptor superfamily, the PPARs have a modular domain structure consisting of domains A/B, C, D, and E. Each domain is associated with specific functions. 

Fibrates work by reducing apolipoproteins B, C-III (an inhibitor of LPL), and E, and increasing apolipoproteins A-I and A-II through activation of peroxisome proliferator-activated receptors-alpha (PPAR-a), a nuclear receptor involved in cellular function. The changes in these apolipoproteins result in a reduction in triglyceride-rich lipoproteins (VLDL and IDL) and an increase in HDL. 

Hu, K. Q., Y. Wang, R. M. Russell, and X. D. Wang. 2008. Apo-lO -lycopenoic acid functions as a peroxisome proliferator-activated receptor gamma activator and inhibits cell growth both in vitro and in ob/ ob mice treated with diethylnitrosamine. In American Association of Cancer Research Annual Meeting. San Diego, CA. 

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. 

S, Papiha SS, Dai R, et al. The human peroxisome proliferator-activated receptor alpha gene identification and functional characterization of two natural allelic variants. Pharmacogenetics 2000 10 321-333. 

Both MOZ and MORF have also been linked to control of transcription. In initial analyses, these MYST HATs were found to contain potent trans-activation domains in their C-termini (Champagne et al, 1999 2001). Follow-up studies demonstrated that the two proteins can indeed function as transcriptional co-activators for two Runt-domain transcription factors - Runxl and 2 (also referred to as AMLl 3) (Kitabayashi et al., 2001a Pelletier et al., 2002). Furthermore, MORF has been found in the co-activator complex associated with the peroxisome proliferator-activated receptor alpha in rat liver (Surapureddi et al., 2002). 

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... 

Tugwood, JD., Holden, P.R., James, N.H., Prince, R.A. Roberts, R.A. (1998) Isolation and characterization of a functional peroxisome proliferator-activated receptor-alpha from guinea pig. Toxicol., 72, 169-177... 

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. 

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. 

Escher, P., and Wahli, W. (2000). Peroxisome proliferator-activated receptors Insight into multiple cellular functions. Mutat. Res. 448, 121-138. 

Peters JM, Taubeneck MW, Keen CL, et al. 1997b. Di(2-ethylhexyl)phthalate induces a functional zinc deficiency during pregnancy and teratogenesis that is independent of peroxisome proliferator-activated receptor-. Teratology 56 311-316. 

Tugwood JD, Aldridge TC, Lambe KG, etal. 1996. Peroxisome proliferator-activated receptors Structures and function. Ann N Y Acad Sci 804 252-265. 

Sher, T., Yt H. F McBride, O. W., and Gonzalez, F. J. (1993). cDNA Cloning, Chromosomal Mapping, and Functional Characterization of the Human Peroxisome Proliferator Activated Receptor. Biochemistry 32, 5598-5604. 

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. 

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). 

Hollenbcrg, A. N., Susulc, V. S., Madura, J. P., Ahang, B, MoUer, D, E.,Tontonoz, R, Sarraf, K Spiegelman, B, M., and Lowell, 0, 0. (1997). Functional antagonism between CCA AT/enhancer binding protoin-a and peroxisome proliferator-activated receptor-y on the leptin promoter. /. Bid. Otem. 272, 5283-5290. 

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