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PGC-1β(过氧化物酶体增殖物激活受体 γ共激活因子 1β)的分子特征及其在团头鲂()中线粒体生物发生中的作用。

Molecular Characterization of PGC-1β (PPAR Gamma Coactivator 1β) and its Roles in Mitochondrial Biogenesis in Blunt Snout Bream ().

机构信息

Laboratory of Fish Nutrition and Physiology, Fisheries College, Jimei University, Xiamen 361021, China.

Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/ II, 389 25 Vodnany, Czech Republic.

出版信息

Int J Mol Sci. 2020 Mar 12;21(6):1935. doi: 10.3390/ijms21061935.

Abstract

This study aimed at achieving the molecular characterization of peroxisome proliferator-activated receptor-gamma coactivator 1β (PGC-1β) and exploring its modulatory roles in mitochondria biogenesis in blunt snout bream (). A full-length cDNA of was cloned from liver which covered 3110 bp encoding 859 amino acids. The conserved motifs of PGC-1β family proteins were gained by MEME software, and the phylogenetic analyses showed motif loss and rearrangement of in fish. The function of PGC-1β was evaluated through overexpression and knockdown of PGC-1β in primary hepatocytes of blunt snout bream. We observed overexpression of along with enhanced mitochondrial transcription factor A () expression and mtDNA copies in hepatocytes, and its knockdown led to slightly reduced expression. However, knockdown of PGC-1β did not significantly influence expression or mtDNA copies. The alterations in mitochondria biogenesis were assessed following high-fat intake, and the results showed that it induces downregulation of . Furthermore, significant decreases in mitochondrial respiratory chain activities and mitochondria biogenesis were observed by high-fat intake. Our findings demonstrated that overexpression of PGC-1β induces the enhancement of TFAM expression and mtDNA amount but not NRF-1. Therefore, it could be concluded that PGC-1β is involved in mitochondrial biogenesis in blunt snout bream but not through PGC-1β/NRF-1 pathway.

摘要

本研究旨在实现过氧化物酶体增殖物激活受体γ共激活因子 1β(PGC-1β)的分子特征,并探讨其在钝吻鲟()线粒体生物发生中的调节作用。从肝脏中克隆出全长 cDNA,长度为 3110bp,编码 859 个氨基酸。MEME 软件获得了 PGC-1β家族蛋白的保守基序,系统发育分析表明,在鱼类中,PGC-1β发生了基序缺失和重排。通过过表达和敲低钝吻鲟原代肝细胞中的 PGC-1β来评估其功能。我们观察到 PGC-1β的过表达伴随着线粒体转录因子 A()表达和肝细胞中线粒体 DNA 拷贝的增强,而其敲低导致表达略有降低。然而,PGC-1β的敲低并未显著影响表达或 mtDNA 拷贝。在高脂肪摄入后评估线粒体生物发生的变化,结果表明它诱导下调。此外,高脂肪摄入导致线粒体呼吸链活性和线粒体生物发生的显著降低。我们的研究结果表明,PGC-1β的过表达诱导 TFAM 表达和 mtDNA 量的增加,但不是 NRF-1。因此,可以得出结论,PGC-1β参与了钝吻鲟的线粒体生物发生,但不是通过 PGC-1β/NRF-1 途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4056/7139572/2c0c0af381b7/ijms-21-01935-g001.jpg

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