Peroxisome proliferator-activated receptor alpha protein

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). 

Tugwood, J.D., Holden, P.R., James, N.H., Prince, R.A. Roberts, R.A. (1998) A peroxisome proliferator-activated receptor-alpha (PPARa) cDNA cloned from guinea-pig liver encodes a protein with similar properties to the mouse PPARa implications for species differences in responses to peroxisome proliferators. Arch. Toxicol., 72, 169-177 Turner, J.H., Petricciani, J.C., Crouch, M.L. Wenger, S. (1974) An evaluation of the effects of diethylhexyl phthalate (DEHP) on mitotically capable cells in blood packs. Transfusion, 14, 560-566... 

Moffit JS, Aleksunes LM, Maher JM, et al. Induction of hepatic transporters multidrug resistance-associated proteins (Mrp) 3 and 4 by clofibrate is regulated by peroxisome proliferator-activated receptor alpha. J Pharmacol Exp Ther 2006 317 537-545. 

Miyata KS, McCaw SE, Meertens LM, Patel HV, Rachubinski RA, Capone J. 1998. Receptor interacting protein 140 interacts with and inhibits transactivation by peroxisome proliferator-activated receptor alpha and liver-X-receptor alpha. Mol. Cell. Endocrinol. 146 69-76... 

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). 

Tanaka, N., Moriya, K., Kiyosawa, K., Koike, K., and Aoyama, T. (2008a). Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice implications for HCV-assodated hepatocarcinogenesis. Int J Cancer 122, 124-131. 

Ellinghaus, P., Wolfrum, C., Assmann, G., Spener, F., and Seedorf, U. Phytanic acid activates the peroxisome proliferator-activated receptor alpha (PPARalpha) in sterol carrier protein 2-j sterol carrier protein x-deficient mice. J Biol Chem 274 (1999) 2766-2772. 

Woifrum, C., Borrmann, C. M., Borchers, T., and Spener, F. Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors alpha - and gamma-mediated gene expression via liver fatty acid binding protein a signaling path to the nucleus. Proc Natl Acad Sci U S A 98 (2001) 2323-2328. 

Abbreviations FASN, fatty acid synthase ACC, acetyl-CoA-carboxylase ACL, ATP-citrate lyase NADPH, nicotinamide adenine dinucleotide phosphate MAT, malonyl acetyl transferases KS, ketoacyl synthase KR, p-ketoacyl reductase DH, p-hydroxyacyl dehydratase ER, enoyl reductase TE, thioesterase ACP, acyl carrier protein VLCFA, very long chain fatty acids ELOVL, elongation of very long chain fatty acids SCDl, stearoyl-CoA desaturase-1 AMPK, AMP-activated kinase ME, malic enzyme FASKOL, liver-specific deletion of FAS PPARa, Peroxisome Proliferator-Activating Receptor alpha HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA SREBP, sterol response element binding protein SIP, site-one protease S2P, site-two... 

Fig. 6. Coordinated transcriptional regulation of fatty acid desaturases and elongases in mammals. PUFA, polyunsaturated fatty acids +, stimulation inhibition LXR, liver X receptor RXR retinoid X receptor SREBP, sterol regulatory element binding protein ChREBP, carbohydrate response element binding protein Mix, Max-like receptor PPAR-ot, peroxisome proliferator activated receptor alpha LXRE, liver X receptor response element SRE, sterol response element ChoRE, carbohydrate response element PPRE, peroxisome proliferator response element. (See color plate section, plate no. 6.)...

A. Mechanism and Effects Fibric acid derivatives (eg, gemfibrozil, fenofibrate, clofibrate) are ligands for the peroxisome proliferator-activated receptor-alpha (PPAR-a) protein, a receptor that regulates transcription of genes involved in lipid metabolism. Tbis interaction with PPAR-a results in increased activity of lipoprotein lipase and enhanced clearance of triglyceride-rich lipoproteins (Figure 35-2). Cholesterol biosynthesis in the liver is seeondarily reduced. The fibrates reduce serum triglyceride concentrations (Table 35-3). There may be a small reduction in LDL cholesterol and a small increase in HDL levels. 

Chu, R., Lim, H., Brumfield, L., Liu, H., Herring, C., Ulintz, P., Reddy, J. K., and Davison, M. (2004) Protein profiling of mouse livers with peroxisome proliferator-activated receptor alpha activation. Mol Cell Biol 24, 6288-97. 

Fenofibrate (propan-2-yl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate), a fibric acid derivative (Fig. 7.6), mainly exerts its effect via the activation of speciflc nuclear receptor called peroxisome proliferator-activated receptor alpha (PPARa). This PPARa agonist is primarily used to decrease the cholesterol levels in cardiovascular diseases patients. Like statins, fenofibrate also reduces triglycerides and low- and very low density protein levels. It also increases high-density lipoprotein levels in the body. Fenofibrate also has nonlipid (i.e., pleiotropic) effects (reduction in fibrinogen, C-reactive protein, and uric acid levels and improvement in the flow-mediated dilatation). 

S. et al. Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. 2000, 87(6), 516-21. 

Yoshikawa T, Ide T, Shimano H, Yahagi N, Amemiya-Kudo M, Matsuzaka T, Yatoh S, Kitamine T, Okazaki H, Tamura Y, et al. Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-Ic promoter through inhibition of LXR signaling. Mol. Endocrinol. 2003 17 1240-1254. 

Abbreviations AA arachidonic acid AFA alpha-linolenic acid AP-1 activator protein 1 COX cyclooxygenase DFIA docosahexaenoic acid EPA eicosapentaenoic acid IF interleukin FA linoleic acid FOX lipoxygenase EPS lipopolysaccaride FT leukotriene NF-kB nuclear factor-kappa B, PG prostaglandin PPARs peroxisome proliferator-activated receptors PUFA polyunsaturated fatty acids, RvEl resolvin El, TNFa tumor necrosis factor alpha, TX thromboxane... 

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