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Review
. 2010 Apr 16:8:e002.
doi: 10.1621/nrs.08002.

PPARalpha: energy combustion, hypolipidemia, inflammation and cancer (V体育安卓版)

Sean R Pyper  1 , Navin Viswakarma, Songtao Yu, Janardan K Reddy
Affiliations
Review

PPARalpha: energy combustion, hypolipidemia, inflammation and cancer

Sean R Pyper et al. Nucl Recept Signal. .

Abstract

The peroxisome proliferator-activated receptor alpha (PPARalpha, or NR1C1) is a nuclear hormone receptor activated by a structurally diverse array of synthetic chemicals known as peroxisome proliferators VSports手机版. Endogenous activation of PPARalpha in liver has also been observed in certain gene knockout mouse models of lipid metabolism, implying the existence of enzymes that either generate (synthesize) or degrade endogenous PPARalpha agonists. For example, substrates involved in fatty acid oxidation can function as PPARalpha ligands. PPARalpha serves as a xenobiotic and lipid sensor to regulate energy combustion, hepatic steatosis, lipoprotein synthesis, inflammation and liver cancer. Mainly, PPARalpha modulates the activities of all three fatty acid oxidation systems, namely mitochondrial and peroxisomal beta-oxidation and microsomal omega-oxidation, and thus plays a key role in energy expenditure. Sustained activation of PPARalpha by either exogenous or endogenous agonists leads to the development of hepatocellular carcinoma resulting from sustained oxidative and possibly endoplasmic reticulum stress and liver cell proliferation. PPARalpha requires transcription coactivator PPAR-binding protein (PBP)/mediator subunit 1(MED1) for its transcriptional activity. .

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Figures

Figure 1
Figure 1. Schematic view of the PPARα structure.
Domain structure of the PPARα protein (A) with the ligand-independent activation function 1 (AF1) domain or A/B domain shown in blue, the DNA-binding domain (DBD) or C domain shown in yellow, the hinge or D domain shown in orange, and the ligand-binding domain (LBD) or E domain together with the activation function 2 (AF2) or F domain shown in green. (B) Schematic representation of the PPARα protein with phosphorylation sites labeled with yellow stars, the corepressor site labeled with a red circle, and the coactivator binding site shown with a blue hexagon.
Figure 2
Figure 2. Biological ligands of PPARα.
Diagram illustrating different known biological ligands of PPARα. Metabolic sources for ligands are grouped in the boxes together with ligand generating enzymes marked with an asterisk, ligands marked with a square and ligand degrading enzymes marked with a triangle. The PPARα and RXRα heterodimer are shown bound to a PPRE sequence in the promoter of a target gene with associated coactivator proteins forming a complex with the cellular transcription machinery.
Figure 3
Figure 3. Levels of regulation of PPARα-mediated transcription.
Diagram illustrating the different factors which regulate the ability of PPARα to activate or repress transcription of target genes. Five major levels of regulation are: (1) the ligand, (2) the receptor expression, (3) the promoter, (4) the coactivator proteins and (5) the expression of target genes.
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References

    1. Antonson P., Schuster G. U., Wang L., Rozell B., Holter E., Flodby P., Treuter E., Holmgren L., Gustafsson J. A. Inactivation of the nuclear receptor coactivator RAP250 in mice results in placental vascular dysfunction. Mol Cell Biol. 2003;23:1260–8. - PMC (VSports在线直播) - PubMed
    1. Aoyama T., Peters J. M., Iritani N., Nakajima T., Furihata K., Hashimoto T., Gonzalez F. J. Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor α (PPARalpha) J Biol Chem. 1998;273:5678–84. - PubMed
    1. Arzuaga X., Reiterer G., Majkova Z., Kilgore M. W., Toborek M., Hennig B. PPARalpha ligands reduce PCB-induced endothelial activation: possible interactions in inflammation and atherosclerosis. Cardiovasc Toxicol. 2007;7:264–72. - PubMed
    1. Barger P. M., Browning A. C., Garner A. N., Kelly D. P. p38 mitogen-activated protein kinase activates peroxisome proliferator-activated receptor α: a potential role in the cardiac metabolic stress response. J Biol Chem. 2001;276:44495–501. - VSports - PubMed
    1. Bays H., Stein E. A. Pharmacotherapy for dyslipidaemia--current therapies and future agents. Expert Opin Pharmacother. 2003;4:1901–38. - PubMed