Auraptene, a citrus fruit compound, regulates gene expression as a PPARα agonist in HepG2 hepatocytes
Auraptene, a citrus fruit compound, regulates gene expression as a PPARα agonist in HepG2 hepatocytes
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DOI：
10.1002/biof.5520330103
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发表时间：
2008-01-01
期刊：
影响因子：
6
通讯作者：
Kawada, Teruo
中科院分区：
文献类型：
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作者：
Takahashi, Nobuyuki;Kang, Min-Sook;Kawada, Teruo
柑橘类水果化合物具有改善许多组织中的病理状况的各种活性。在这项研究中，我们研究了柑橘皮中主要含有的橙皮素对过氧化物酶体增殖物激活受体α（PPAR α）激活的影响。为了检测金萝卜素对肝细胞中的PPAR α活化的影响，使用HepG 2肝细胞开发了PPAR配体测定系统，其中内源性PPAR α表达水平非常低。在过氧化物酶体增殖物激活受体配体测定中，添加金萝卜素显示出以剂量依赖性方式对GAL 4/过氧化物酶体增殖物激活受体α嵌合体蛋白的反式激活的显著影响。实际上，在表达PPAR α的HepG 2肝细胞中，用金萝卜素处理诱导了PPAR靶基因的上调，如酰基辅酶A氧化酶（ACO）、肉毒碱棕榈酰转移酶1A（CPT 1A）和酰基辅酶A合成酶（ACS）。基因表达的调节依赖于PPAR α，因为模拟转染的HepG 2肝细胞没有显示出调节。通过金萝卜素上调PPAR靶基因表达足以增强油酸摄取到表达PPAR α的HepG 2肝细胞中。这些结果表明，金萝卜素在肝细胞中充当PPARalpha激动剂，并且金萝卜素可以通过肝脏中的PPARalpha活化来改善脂质异常。
Citrus fruit compounds have various activities that improve pathological conditions in many tissues. In this study, we examined the effect of auraptene contained mainly in the peel of citrus on peroxisome proliferator-activated receptor-alpha (PPAR alpha) activation. To examine effects of auraptene on the PPAR alpha activation in hepatocytes, PPAR ligand assay system was developed using HepG2 hepatocytes, in which the endogenous PPAR alpha expression level is very low. In the PPAR ligand assay, the addition of auraptene showed significant effects on the transactivation of GAL4/PPAR alpha chimera proteins in a dose-dependent manner. Actually, treatment with auraptene induced the up-regulation of PPAR target genes, such as acyl-CoA oxidase (ACO), carnitine-palmitoyl transferase 1A (CPT1A) and acyl-CoA synthetase (ACS), in PPAR alpha-expressing HepG2 hepatocytes. The regulation of gene expression was dependent on PPAR alpha because mock-transfected HepG2 hepatocytes showed no regulation. The up-regulation of PPAR target gene expression by auraptene was sufficient to enhance oleic acid uptake into PPAR alpha-expressing HepG2 hepatocytes. These results indicate that auraptene acts as a PPAR alpha agonist in hepatocytes and that auraptene may improve lipid abnormality through PPAR alpha activation in the liver.