Involvement of PI3K/Akt/TOR pathway in stretch-induced hypertrophy of myotubes

笹井, 宣昌; SASAI, NOBUAKI

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Involvement of PI3K/Akt/TOR pathway in stretch-induced hypertrophy of myotubes

http://hdl.handle.net/2237/14436

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	k8665.pdf (466.1 kB)

Item type

学位論文 / Thesis or Dissertation(1)

公開日

2011-01-20

タイトル

Involvement of PI3K/Akt/TOR pathway in stretch-induced hypertrophy of myotubes

その他のタイトル

伸張刺激により引き起こされる筋管細胞肥大への PI3K/Akt/TOR 経路の関与

著者

笹井, 宣昌

SASAI, NOBUAKI

キーワード

主題Scheme

Other

主題

Akt

キーワード

主題Scheme

Other

主題

cultured cells

キーワード

主題Scheme

Other

主題

cyclic stretching

キーワード

主題Scheme

Other

主題

ERK

キーワード

主題Scheme

Other

主題

muscle hypertrophy

抄録

内容記述

Skeletal muscle cells are hypertrophied by mechanical stresses, but the underlying molecular mechanisms are not fully understood. Two signaling pathways, phosphatidylinositol 3-kinase (PI3K)/Akt to target of rapamycin (TOR) and extracellular signal-regulated kinase kinase (MEK) to extracellular signal-regulated kinase (ERK), have been proposed to be involved in muscle hypertrophy. In this study we examined the involvement of these pathways in primary cultures of chick skeletal myotubes subjected to passive cyclic stretching for 72 hours, a time that was sufficient to induce significant hypertrophy in our preparations. Hypertrophy was largely suppressed by wortmannin or rapamycin, inhibitors of PI3K or mTOR, respectively. Furthermore, phosphorylation of Akt was enhanced by stretching and suppressed by wortmannin. The MEK inhibitor, U0126, exerted a minimal influence on stretch-induced hypertrophy. We found that cyclic stretching of myotubes activates the PI3K/Akt/TOR pathway, resulting in muscle hypertrophy. The MEK/ERK pathway may contribute negatively to spontaneous hypert

内容記述タイプ

Abstract

抄録

内容記述

骨格筋細胞は、機械ストレスにより肥大する。しかしながら、その分子メカニズム
は十分に解明されてない。筋肥大に関与すると考えられている細胞シグナル経路とし
て、 phosphatidylinositol 3-kinase (PI3K)/Akt/target of rapamycin (TOR) 経路や extracellular
signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) 経路がある。
本研究では、それら経路が、筋細胞の伸張刺激による肥大に関連するかどうかという
点について調べた。トリ胸筋の初代培養による成熟した筋管細胞に、その長軸方向の
周期的伸張（伸張率 10%, 1/6 Hz, 72 時間）を加えたところ、伸張しない細胞に比べ太
さが約 1.6 倍に肥大した (p < 0.05)。この伸張刺激による肥大は、 PI3K の阻害剤
(wortrmannin) や、 TOR の阻害剤 (rapamycin) により抑制された。さらに伸張刺激を 5
及び 60 分加えた細胞のリン酸化 Akt の割合は、刺激前に比べ凡そ 2.5 倍高かった
(p < 0.05)。このシグナル亢進は wortrmannin により抑制された。一方、 MEK の阻害
剤 (U0126) により、伸張刺激に関わらず細胞は肥大した。伸張刺激による肥大は殆ど
変わらなかった。これらの結果から、伸張刺激による筋管細胞肥大に対し
PI3K/Akt/TOR 経路が関連することや、 ERK の関連は僅かであることが示唆された。
さらに ERK が、成熟した筋管の太さ制御に負に関わることも示唆された。

内容記述タイプ

Abstract

内容記述

名古屋大学博士学位論文学位の種類:博士(リハビリテーション療法学) (課程) 学位授与年月日　平成22年3月25日

内容記述タイプ

Other

言語

eng

資源タイプ

資源

http://purl.org/coar/resource_type/c_46ec

タイプ

thesis

書誌情報

発行日 2010-03-25

学位授与年度

2009

学位授与年月日

2010-03-25

学位授与番号

13901甲第8665号

著者版フラグ

値

publisher

URI

識別子

http://hdl.handle.net/2237/14436

識別子タイプ

HDL

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Involvement of PI3K/Akt/TOR pathway in stretch-induced hypertrophy of myotubes

× 笹井, 宣昌

× SASAI, NOBUAKI

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