Characterization of Paralichthys olivaceus peroxisome proliferator-activated receptor-α gene as a master regulator of flounder lipid metabolism
Characterization of Paralichthys olivaceus peroxisome proliferator-activated receptor-α gene as a master regulator of flounder lipid metabolism
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DOI：
10.1016/j.ygcen.2011.08.026
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发表时间：
2012-01-01
影响因子：
2.7
通讯作者：
Cheong, JaeHun
中科院分区：
文献类型：
--
作者：
Cho, Hyun Kook;Kong, Hee Jeong;Cheong, JaeHun
过氧化物酶体增殖物激活受体（PPARs）是一种核激素受体，在脂质和能量稳态中起关键作用。采用RT-PCR和RACE技术，从不同鱼类中的保守序列中克隆了牙鲆过氧化物酶体增殖物激活受体α（PopPPARalpha）的cDNA。PoPPAR α cDNA全长2040 bp，编码505个氨基酸，含有一个DNA结合结构域（C4型锌指）和一个配体结合结构域。PopPAR α从孵化后1天开始检测，并在连续喂养的比目鱼（约16 cm大小）的胃、肝和肠中高度表达。在30天的食物剥夺期后，4.5个月大的比目鱼的肾脏、胃和肝脏中的POPPAR α mRNA表达下调。PoPPARalpha激活PPARresponseelement（PPRE）驱动的报告基因，并且用PPARalpha激动剂Wy 14643处理增强了HINAE和HepG 2细胞中PoPPARalpha刺激的过氧化物酶体增殖物应答元件活性。PoPPAR α通过竞争性抑制LXR/RXR异源二聚体形成，激活脂肪酸β-氧化相关基因（如肉毒碱棕榈酰转移酶1A、中链酰基辅酶A脱氢酶和酰基辅酶A氧化酶1）的表达，并抑制固醇调节元件结合蛋白和脂肪酸合成酶的表达。这些结果表明，PopPAR α在比目鱼的脂质代谢中起着重要的作用，并且在比目鱼和哺乳动物中具有功能和进化上的保守性。(C)2011年由Elsevier Inc.出版
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that play key roles in lipid and energy homeostasis. Paralichthys olivaceus PPAR alpha (PoPPAR alpha) cDNA was isolated by initial reverse transcription-polymerase chain reaction (RT-PCR) using conserved region among fish species and rapid amplification of cDNA ends (RACE). The full-length of PoPPAR alpha cDNA is 2040-bp long encoding a polypeptide with 505 amino acids and containing a DNA binding domain (C4-type zinc finger) and a ligand-binding domain. PoPPAR alpha was detected from 1 day post-hatch and was highly expressed in the stomach, liver, and intestine of continuously fed flounder, approximately 16 cm in size. PoPPAR alpha mRNA expression was down-regulated in the kidney, stomach, and liver of the 4.5-month-old flounder after a 30 day food-deprivation period. PoPPAR alpha activates the PPAR response element (PPRE)-driven reporter, and treatment with Wy14643, a PPAR alpha agonist, augmented PoPPAR alpha-stimulated peroxisome proliferator response element activity in HINAE and HepG2 cells. PoPPAR alpha activated the expression of fatty acid beta-oxidation related genes such as carnitine palmitoyltransferase 1A, medium chain acyl-CoA dehydrogenase, and acyl-CoA oxidase 1 and inhibited the expression of sterol regulatory element binding protein and fatty acid synthase by competitively inhibiting LXR/RXR heterodimer formation. These results suggest that PoPPAR alpha plays an important role in lipid metabolism of olive flounder and that it is functionally and evolutionarily conserved in olive flounder and mammals. (C) 2011 Published by Elsevier Inc.