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完全的GPR40激动剂AM1638通过AMPK依赖的通路缓解了H9c2细胞中棕酸盐诱导的氧化损伤

SukHwan Yun¹, Joo Won Kim¹, Min Jeong Park²

¹BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Korea.

|January 5, 2025

概括

作为G蛋白结合受体40 (GPR40) agonist,AM1638通过减少氧化应激来保护心脏细胞免受脂肪酸损伤. 这种有益的效果取决于腺单酸盐激活蛋白激酶 (AMPK) 的激活.

科学领域:

心血管生物学心血管生物学
代谢信号传递代谢信号传递
氧化压力研究研究氧化压力研究

背景情况:

G蛋白结合受体40 (GPR40) 涉及代谢障碍,但其在心肌细胞中的作用尚不清楚.
像palmitate这样的脂肪酸可以诱导氧化应激和损伤心脏细胞.
了解GPR40在心脏中的功能对于开发新的治疗策略至关重要.

研究的目的:

为了研究GPR40主激素AM1638对H9c2大鼠心肌细胞的Palmitate诱导损伤的保护作用.
阐明潜在的分子机制,包括腺单酸活性蛋白激酶 (AMPK) 的参与.

主要方法:

用AM1638和palmitate对H9c2细胞进行治疗.
评估AMPK酸化,抗氧化基因表达 (HO-1,NQO1) 和氧化应激标志物 (超氧化物,4-HNE).
评估线粒体功能 (膜潜力,ATP产生) 和亡标志物 (caspase-3裂变,核分裂).
使用化合物C抑制AMPK以确定途径依赖性.

主要成果:

AM1638治疗增加了AMPK酸化和抗氧化基因HO-1和NQO1.1的表达.
AM1638降低了棕酸盐诱导的超氧化物产生和4-氨酸的水平.
由palmitate引起的线粒体功能障碍和ATP枯竭被AM1638.8逆转.
AM1638抑制了棕酸盐诱导的亡,改善了细胞活力.
AM1638的保护作用被AMPK抑制剂C化合物所取消.

结论:

作为GPR40激动剂的AM1638有效地改善了棕酸盐诱导的氧化应激和心肌细胞中的细胞损伤.
保护机制涉及AMPK信号通路的激活.
激活GPR40代表了一种潜在的治疗点,用于保护心脏免受脂毒性.

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