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https://doi.org/10.24546/81003702
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2024-04-19
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81003702 (fulltext)
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81003702
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open access
出版タイプ
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タイトル
Regulation of SREBP1c Expression by mTOR Signaling in Hepatocytes
著者
Takashima, Mototsugu ; Ogawa,Wataru ; Emi, Aki ; Kasuga,Masato
著者名
Takashima, Mototsugu
著者名
Ogawa,Wataru
著者名
Emi, Aki
著者名
Kasuga,Masato
収録物名
The Kobe journal of the medical sciences
巻(号)
55(2)
ページ
45-52
出版者
神戸大学医学部
Kobe University School of Medicine
刊行日
2009-04
公開日
2011-12-05
抄録
The transcription factor sterol regulatory element binding protein 1c (SREBP1c) plays an important role in the regulation of fatty acid metabolism in the liver. Although the importance of phosphoinositide 3-kinase in the regulation of SREBP1c expression is widely accepted, the role of mammalian target of rapamycin (mTOR) in such regulation has remained unclear. We have now shown that the insulin-induced increase in the abundance of SREBP1c mRNA in cultured AML12 mouse hepatocytes was largely abolished by LY294002, an inhibitor of phosphoinositide 3-kinase, but was reduced only slightly by rapamycin, an inhibitor of mTOR. Forced expression of a constitutively active form of Akt containing a myristoylation signal sequence (MyrAkt) in these cells with the use of an adenoviral vector resulted in the phosphorylation of p70 S6 kinase, a downstream target of mTOR signaling, and this effect was inhibited by rapamycin. MyrAkt also increased the abundance of SREBP1c mRNA and protein as well as the expression of the SREBP1c target genes for fatty acid synthase and stearoyl-CoA desaturase 1. These effects of MyrAkt were also markedly inhibited by LY294002 and by rapamycin. These results thus suggest that mTOR signaling plays a major role in Akt-mediated up-regulation of SREBP1c expression but that it plays only a minor role in insulin-induced expression of this transcription factor.
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The Kobe journal of the medical sciences
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55巻
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55巻2号(2009-04)
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資源タイプ
departmental bulletin paper
言語
English (英語)
ISSN
0023-2513
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NCID
AA00711740
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http://www.med.kobe-u.ac.jp/journal/contents.html
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