增强线粒体的pyruvate代谢改善心肌缺血再流损伤
bioRxiv : the preprint server for biology
|February 14, 2024
概括
抑制单碳酸盐载体4 (MCT4) 通过正常化新陈代谢来保护心脏免受缺血-再输液 (I/R) 损伤. 这种方法改善了心肌回收和心脏功能后的再注血,提供了一个新的治疗策略.
科学领域:
- 心血管科学 心血管科学
- 代谢医学是一种代谢医学.
- 细胞生物学 细胞生物学
背景情况:
- 初级穿皮冠状动脉干预 (PPCI) 治疗急性心肌梗塞,但可能导致缺血-再输液 (I/R) 损伤,大大导致心肌损伤.
- 目前的临床干预措施缺乏减轻I/R损伤的能力,需要新的治疗策略.
研究的目的:
- 调查酸乳酸代谢轴在I/R损伤后心肌恢复中的作用.
- 为了确定抑制MCT4是否可以减少I/R损伤并改善心脏功能.
主要方法:
- 在后I/R损伤模型中研究了线粒体的酸盐载体 (MPC) 和MCT4表达.
- 使用了选择性MCT4抑制剂 (VB124) 在再注射时给予.
- 评估了反应性氧物种 (ROS),线粒体膜潜力,Ca2+水平,pyruvate氧化,心肌挽救和功能结果.
主要成果:
- 观察到MPC上调是在I/R后存活的心肌中,而MPC损失增加了细胞死亡和MCT4上调.
- 药理上抑制MCT4与VB124正常化的ROS,线粒体潜力和Ca2+水平.
- 抑制MCT4增强了pyruvate进入TCA循环的作用,改善了心肌救援和心脏功能.
结论:
- 酸盐-乳酸盐代谢轴对于在I/R损伤后确定心肌救援至关重要.
- 向MCT4代表了一种有前途的药理学策略,以减轻I / R损伤和保持心脏功能.
相关概念视频
01:15Pyruvate Oxidation
After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
01:20Fates of Pyruvate
Pyruvate is the end product of glycolysis, where glucose is oxidized to pyruvate, simultaneously reducing NAD+ to NADH. Two molecules of ATP are also produced by substrate-level phosphorylation.
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
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Cells of Liver
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