Abstract
Peroxisome proliferator-activated receptors, PPARs, are members of nuclear hormone recptor superfamily implicated in energy homeostatis including lipid metabolism. On activation by binding of ligand, these ligand-PPARs complexes as transcription factors stimulated gene expression by binding to the promoter of target genes. The different structural domains of PPARs are present in terms of activation mechanisms, namely ligand binding-, phosphorylation-and cofactor interaction-domain, PPAR has three isoforms, a, /3 (5) and y, and each isoform shows different ligand specificity and tissue distribution. In ligands activating PPARs many structural divers compounds, such as fatty acids, eicosanoids, hypolipidemic drugs and thiazolidinediones (TZD) are involved. Threfore, it has been recognized that PPARs relate to cellular energy homeostasis as a regulatory factor of lipid metabolism. The name, PPAR is originated from “peroxisome proliferators”. Peroxisome proliferators are a large group of chemicals which, when fed to rodents, results in a characteristic hepatomegaly, peroxisome proliferation in parenchymal cells, and induction of non-genotoxic hepatocarcinoma. As a mechanim of peroxisome proliferator-induced carcinogenesis, oxidative stress and disruption of the regulation of cell growth/development process has been noticed. Now, it is elucidated that PPAR plays an essential role in peroxisome proliferator-induced hepatocarcinogenesis through the study using a knockout mouse.
