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大学・研究所にある論文を検索できる 「栄養失調の骨格筋における酸化ストレス過剰表現とAMPK/SIRT1のエネルギーセンシングを介した速筋と遅筋の代謝能の低下」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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栄養失調の骨格筋における酸化ストレス過剰表現とAMPK/SIRT1のエネルギーセンシングを介した速筋と遅筋の代謝能の低下

Hirabayashi, Takumi 平林, 卓己 ヒラバヤシ, タクミ 神戸大学

2021.03.25

概要

栄養失調は骨格筋量の減少だけではなく,骨格筋の代謝能の低下も引き起こす.栄蓑失調の骨格筋では速筋が優位に減少するが,速筋と遅筋の代謝能の違いは知られていない.また,栄養失調時の骨格筋における代謝能の低下は低アルプミン血症に伴う酸化ストレスの増加やエネルギーセンシング因子の変化が関与していることが予想される.本研究では,1)栄養失調時の骨格筋における速筋と遅筋の代謝能の違いを評価し,2)栄養失調に伴う酸化ストレスとAMPK/SIRTlのエネルギーセンシングの変化を検証した.

雄性Wistar系ラット(454士6g)を対照群(n=6)と栄養失調群(n=6)に区分した.対照群には14%カゼインを含む通常飼料を与えた.栄養失調群には5%カゼインに調整した低タンパク質飼料を与え,1日あたりの摂取量を通常時の50%に制限して栄養失調を誘発させた.12週間後に足底筋(速筋),ヒラメ筋(遅筋)およぴ血液を採取して解析に用いた.酸化ストレスは骨格筋内の主要なミトコンドリア抗酸化酵素であるSOD-2タンパク質や血漿中のスーパーオキシドを指標とし,エネルギーセンシング応答は骨格筋内のAMPKとSIRTIタンパク質およびその下流因子であるPGC-1aとPINKIタンパク質を指標とした.また,骨格筋の代謝能は主要なクエン酸回路内酵素(クエン酸合成酵素,コハク酸脱水素酵素)の活性およびミトコンドリア呼吸鎖酵素であるCOXIVタンパク質で評価した.

栄養失調は足底筋の筋重量と筋線維横断面積の減少をもたらしたが,ヒラメ筋では変化しなかった.栄養失調は血漿中の抗酸化物質であるアルブミン濃度を減少させ,血漿中のスーパーオキシド濃度を増加させた.骨格筋内ではSOD-2タンパク質が栄養失調群の両骨格筋で減少し,栄養失調に伴うミトコンドリアの抗酸化能の低下が観祭された.また,栄養失調は両骨格筋におけるAMPKのリン酸化を促進した.一方,栄養失調群の両骨格筋でSIRTI発現は減少し,PGC-1aとPINKl発現も減少した.さらにクエン酸合成酵素とコハク酸脱水素酵素の活性レベルおよぴCOXIV発現は栄養失調群の両骨格筋で減少し,栄養失調時は速筋と遅筋の両方で骨格筋の代謝能が低下することを確認した.

本研究の結果から栄養失調時は筋蓋の減少が生じにくい遅筋でも骨格筋の代謝能が低下することが明らかになった.また,栄養失調はSIRTlの抑制を介して骨格筋の代謝能を低下させることを示すことができた.

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