Cook W S, Yeldandi A V, Rao M S, Hashimoto T, Reddy J K
Department of Pathology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611-3008, USA.
Biochem Biophys Res Commun. 2000 Nov 11;278(1):250-7. doi: 10.1006/bbrc.2000.3739.
The peroxisome proliferator-activated receptor alpha (PPAR alpha) is a nuclear receptor that transcriptionally regulates mitochondrial and peroxisomal fatty acid beta-oxidation enzymes in the liver. Ligands include synthetic peroxisome proliferators and some fatty acids. PPARalpha activation leads to predictable pleiotropic responses in liver including peroxisome proliferation, increased fatty acid oxidation, and hepatocellular carcinoma. In the current study, the response to PPAR alpha-activation was compared in the heart, kidney, and liver since the role of PPAR alpha in extrahepatic fatty acid-oxidizing organs has not been fully explored. Basal expression of mitochondrial beta-oxidation enzymes was comparable in the three tissues, but peroxisomal beta-oxidation enzymes were most abundant in the liver and less so in the kidney and especially in the heart. After PPAR alpha activation with ciprofibrate, both mitochondrial and peroxisomal beta-oxidation enzymes were induced, with the strongest response seen in the liver, a moderate response in the kidney, and no significant response in the heart. PPAR alpha mRNA analysis suggested that the differential response may be related to PPAR alpha expression.
过氧化物酶体增殖物激活受体α（PPARα）是一种核受体，可转录调控肝脏中的线粒体和过氧化物酶体脂肪酸β-氧化酶。其配体包括合成过氧化物酶体增殖物和一些脂肪酸。PPARα激活会在肝脏中引发可预测的多效性反应，包括过氧化物酶体增殖、脂肪酸氧化增加以及肝细胞癌。在当前研究中，对心脏、肾脏和肝脏中PPARα激活的反应进行了比较，因为PPARα在肝外脂肪酸氧化器官中的作用尚未得到充分探索。线粒体β-氧化酶的基础表达在这三个组织中相当，但过氧化物酶体β-氧化酶在肝脏中最为丰富，在肾脏中较少，在心脏中尤其少。在用环丙贝特激活PPARα后，线粒体和过氧化物酶体β-氧化酶均被诱导，其中在肝脏中反应最强，在肾脏中反应中等，在心脏中无明显反应。PPARα mRNA分析表明，这种差异反应可能与PPARα表达有关。
