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Author Hatazawa, Yukino ♦ Minami, Kimiko ♦ Yoshimura, Ryoji ♦ Onishi, Takumi ♦ Manio, Mark Christian ♦ Inoue, Kazuo ♦ Sawada, Naoki ♦ Suzuki, Osamu ♦ Miura, Shinji ♦ Kamei, Yasutomi
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ AMINO ACIDS ♦ GENES ♦ KNOCK-OUT REACTIONS ♦ METABOLISM ♦ MUSCLES ♦ OXIDATION ♦ PERFORMANCE ♦ TRANSCRIPTION FACTORS ♦ TRANSGENIC MICE
Abstract The expression of the transcriptional coactivator PGC1α is increased in skeletal muscles during exercise. Previously, we showed that increased PGC1α leads to prolonged exercise performance (the duration for which running can be continued) and, at the same time, increases the expression of branched-chain amino acid (BCAA) metabolism-related enzymes and genes that are involved in supplying substrates for the TCA cycle. We recently created mice with PGC1α knockout specifically in the skeletal muscles (PGC1α KO mice), which show decreased mitochondrial content. In this study, global gene expression (microarray) analysis was performed in the skeletal muscles of PGC1α KO mice compared with that of wild-type control mice. As a result, decreased expression of genes involved in the TCA cycle, oxidative phosphorylation, and BCAA metabolism were observed. Compared with previously obtained microarray data on PGC1α-overexpressing transgenic mice, each gene showed the completely opposite direction of expression change. Bioinformatic analysis of the promoter region of genes with decreased expression in PGC1α KO mice predicted the involvement of several transcription factors, including a nuclear receptor, ERR, in their regulation. As PGC1α KO microarray data in this study show opposing findings to the PGC1α transgenic data, a loss-of-function experiment, as well as a gain-of-function experiment, revealed PGC1α’s function in the oxidative energy metabolism of skeletal muscles. - Highlights: • Microarray analysis was performed in the skeletal muscle of PGC1α KO mice. • Expression of genes in the oxidative energy metabolism was decreased. • Bioinformatic analysis of promoter region of the genes predicted involvement of ERR. • PGC1α KO microarray data in this study show the mirror image of transgenic data.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-12-09
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 481
Issue Number 3-4


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