酸はmTORの阻害によって低酸素における日経時計を停止する.
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PubMedで要約を見る
まとめ
この要約は機械生成です。腫瘍の酸性により 日常時計が乱され 翻訳が抑制されます ラパミシン複合体1 (mTORC1) のシグナリングのメカニズム的標的の回復は,細胞代謝とタイムキーピングの間のリンクを明らかにし,昼夜リズムを救う.
科学分野
- 細胞生物学
- クロノバイオロジー
- 癌 生物学
背景
- 低酸素症は低酸素誘導因子 (HIF) を通して昼夜時計に影響する.
- 腫瘍の微小環境は 低酸素と酸性によって特徴付けられます
- 昼間の遺伝子発現と細胞のプロセスを制御する.
研究 の 目的
- 腫瘍の微小環境の酸性による 昼夜時計の影響を調べるため
- 酸性,代謝,および昼夜中断を結びつける分子メカニズムを解明する.
主な方法
- 主要なT細胞を含むヒトとネズミの細胞ラインの酸性化
- 昼間振動と昼間トランスクリプトームの評価
- ラパミシン複合体1 (mTORC1) 信号伝達の機械的標的の測定
- リソソームの局所化とmTORとのRHEB相互作用の分析
主要な成果
- 細胞の酸性化は 昼間のトランスクリプトームを大きく乱します
- 酸性のバッファリングや 乳酸の生成を阻害することで 昼夜振動が救われます
- 酸性化によりmTORC1のシグナル伝達が抑制され,ライソソーム再分布を引き起こし,ライソソーム結合 mTORが抑制される.
- mTORC1の信号を復元すると 時計の振動が回復する
結論
- 細胞の代謝が低酸素状態にあるため,腫瘍の酸度が 昼夜時計を抑制する.
- この抑制は,mTORC1のシグナル伝達が阻害されたため,クロック構成要素の翻訳が低下したことで起こります.
- 酸性へのターゲティングまたはmTORC1シグナリングの回復は,がんにおける昼夜リズム障害の治療戦略を提供することができる.
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