POSITIVE REGULATION OF THE PEROXISOMAL BETA-OXIDATION PATHWAY BY FATTY-ACIDS THROUGH ACTIVATION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR)
POSITIVE REGULATION OF THE PEROXISOMAL BETA-OXIDATION PATHWAY BY FATTY-ACIDS THROUGH ACTIVATION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR)
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DOI：
10.1016/s0248-4900(05)80176-5
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发表时间：
1993-01-01
影响因子：
2.7
通讯作者：
WAHLI, W
中科院分区：
文献类型：
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作者：
DREYER, C;KELLER, H;WAHLI, W
过氧化物酶体增殖因子通过激活配体依赖的转录因子来调节基因的转录，由于其结构和功能，这些转录因子可以归属于核激素受体的超家族。三种过氧化物酶体增殖体激活受体（ppar α， β和γ）已在非洲爪蟾中克隆。它们的mrna表达不同；卵母细胞和胚胎中表达xppara和β，但不表达xppara。在成人中，xppara和β的表达似乎是普遍存在的，而xpparγ主要在脂肪组织和肾脏中观察到。免疫细胞化学分析显示ppar是核蛋白，其胞质-核易位不受外源激活剂的影响。PPARs的一个靶基因是编码酰基辅酶A氧化酶（acyl-CoA oxidase， ACO）的基因，该基因催化脂肪酸过氧化物酶体β -氧化的限速步骤。在ACO基因的启动子中发现了一个PPARs与之结合的过氧化物酶体增殖反应元件（PPRE）。除了已知的ppar的外源激活剂，如降血脂药物，天然激活剂已被确定。生理浓度下的多不饱和脂肪酸是ppar的有效激活剂，而花生四烯酸的炔同源物5,8,11,14-二十碳四烯酸（ETYA）是迄今为止所描述的最有效的xppar α激活剂。综上所述，我们的数据表明ppar在脂质代谢中起重要作用。
Peroxisome proliferators regulate the transcription of genes by activating ligand-dependent transcription factors, which, due to their structure and function, can be assigned to the superfamily of nuclear hormone receptors. Three such peroxisome proliferator-activated receptors (PPARalpha, beta, and gamma) have been cloned in Xenopus laevis. Their mRNAs are expressed differentially; xPPARalpha and beta but not xPPARgamma are expressed in oocytes and embryos. In the adult, expression of xPPARalpha and beta appears to be ubiquitous, and xPPARgamma is mainly observed in adipose tissue and kidney. Immunocytochemical analysis revealed that PPARs are nuclear proteins, and that their cytoplasmic-nuclear translocation is independent of exogenous activators. A target gene of PPARs is the gene encoding acyl-CoA oxidase (ACO), which catalyzes the rate-limiting step in the peroxisomal beta-oxidation of fatty acids. A peroxisome proliferator response element (PPRE), to which PPARs bind, has been identified within the promoter of the ACO gene. Besides the known xenobiotic activators of PPARs, such as hypolipidemic drugs, natural activators have been identified. Polyunsaturated fatty acids at physiological concentrations are efficient activators of PPARs, and 5,8,11,14-eicosatetraynoic acid (ETYA), which is the alkyne homolog of arachidonic acid, is the most potent activator of xPPARalpha described to date. Taken together, our data suggest that PPARs have an important role in lipid metabolism.