カンナビノイド受容体2中心分子フィードバックループ 糖尿病性心臓損傷における死滅を誘発する
Pan Gao1, Mengying Cao1, Xueli Jiang1
1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, China (P.G., M.C., X.J., X.W., G.Z., C.Y., J.G., Y.Z.).
Circulation
|November 30, 2022
まとめ
アポトーシス後の糖尿病の心臓機能障害を誘発する プログラム細胞死という形です カンナビノイド受容体2 (CB2R) を標的にすることは,この状態に対する有望な治療戦略です.
科学分野:
- 心血管生物学
- 代謝疾患の研究
- 細胞 死 の 仕組み
背景:
- 糖尿病性心臓機能障害は糖尿病の重大な合併症で 主に細胞死によって引き起こされます
- 糖尿病患者の心臓における細胞死経路の正確なタイミングとシーケンスはまだよくわかっていません.
- 特定の細胞死型と治療的介入点を特定することは,糖尿病性心筋病の治療に不可欠です.
研究 の 目的:
- 糖尿病の心臓機能障害の原因となる 細胞死経路を特定する
- この細胞死経路を制御する 分子メカニズムを解明する
- 糖尿病性心臓病の治療に この経路をターゲットに 新しい治療戦略を提案する
主な方法:
- 1型および2型糖尿病マウスモデル (db/db,HFD/STZ,STZ誘発) を利用した.
- 異なる年齢の糖尿病マウスの心臓におけるアポプトーシスとネクロプトーシスの評価
- Gタンパク質結合受容体薬のライブラリ,薬理学/遺伝的調節,安定した細胞系,および機械学的研究のためのカスタムリン酸化抗体を使用した.
主要な成果:
- 糖尿病の後期段階では,アポプトーシスが活性化され,心臓機能障害を直接引き起こした.
- カンナビノイド受容体2 (CB2R) は死滅の重要な調節因子として特定されました.
- CB2Rは通常,BACH2経由で死滅を抑制し,高血糖はCB2Rの内化を促進し,その後のMLKL媒介によるCB2Rのリン酸化と分解を阻害し,フィードバックループを作成します.
結論:
- CB2RとBACH2を含む新しい分子調節ループが 糖尿病の心臓における死滅を制御する.
- CB2Rの活性化は死滅を抑制し,MLKLの活性化は,CB2Rのリン酸化と分解につながり,負のフィードバックメカニズムを形成します.
- CB2Rを中心とした死滅経路をターゲットにすることで 糖尿病の心臓機能障害の治療戦略が期待されます
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