PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.
PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.
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DOI：
10.1371/journal.pone.0091006
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Miura S
中科院分区：
文献类型：
--
作者：
Hatazawa Y;Tadaishi M;Nagaike Y;Morita A;Ogawa Y;Ezaki O;Takai-Igarashi T;Kitaura Y;Shimomura Y;Kamei Y;Miura S
过氧化物酶体增殖物激活受体（Peroxisome proliferator-activated receptor，PPAR）γ共激活因子1α（PGC-1α）是多种核受体和其他转录因子的共激活因子，参与调节能量代谢、产热等生物学过程，控制包括骨骼肌在内的多种器官系统的表型特征。骨骼肌中的PGC-1α被认为参与收缩蛋白功能、线粒体功能、代谢调节、细胞内信号传导和转录反应。支链氨基酸（BCAA）的代谢主要发生在骨骼肌线粒体中，与BCAA代谢相关的酶通过运动而增加。我们使用过表达PGC-1α的小鼠骨骼肌和培养的细胞，研究PGC-1α是否通过增加参与BCAA代谢的酶的表达来刺激BCAA代谢。在骨骼肌特异性过表达PGC-1α的转基因小鼠，其支链氨基转移酶（BCAT）2和支链α-酮酸脱氢酶（BCKDH）的表达增加，而BCAT 2和BCKDH是BCAA的代谢酶。磷酸化BCKDH并抑制其酶活性的BCKDH激酶（BCKDK）的表达没有变化。与野生型小鼠相比，转基因小鼠骨骼肌中BCAA的量显著降低。转基因小鼠体内BCAA代谢产物谷氨酸含量增加，提示PGC-1α激活了肌肉BCAA代谢。在C2 C12细胞中，PGC-1α过表达可显著增加BCAT 2和BCKDH的表达，但对BCKDK无影响。因此，骨骼肌中的PGC-1α被认为对BCAA代谢有显著贡献。
Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain α-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.
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影响因子：
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通讯作者：
Spiegelman, BM
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通讯作者：
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