对心脏病发作治疗的潜在目标:在MAM中通过GRP75介导的Ca2+转移
Chenyan Zhang1, Bowen Liu1, Jiaxing Sheng1
1School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
European journal of pharmacology
|March 25, 2024
概括
葡萄糖调节蛋白75 (GRP75) 在心脏病发作后影响和线粒体. 抑制GRP75通过调节和降低内质网膜应激来改善细胞存活率.
科学领域:
- 心血管生物学 心血管生物学
- 细胞应激反应的应激反应
- 线粒体动力学的动力学
背景情况:
- 心肌梗塞 (MI) 扰乱了细胞 (Ca2+) 稳定性和线粒体功能,与内质网膜 (ER) 压力有关.
- ER压力加剧了Ca2+干扰和心肌细胞亡后的MI.
- 葡萄糖调节蛋白75 (GRP75) 在心脏病发作后心脏功能障碍中的作用尚不清楚.
研究的目的:
- 研究GRP75在MI Ca2+后恒温和线粒体功能中的作用.
- 为了了解GRP75在ER应激诱导心肌细胞损伤中的参与.
主要方法:
- 利用MI和氧气-葡萄糖剥夺 (OGD) 诱导的心肌细胞的老鼠模型.
- 评估了ER应激激活,Ca2+水平,线粒体功能和亡.
- 进行了GRP75淘汰和转录组分析.
主要成果:
- MI和OGD增加了ER压力和GRP75与IP3R和VDAC1.1的同定位.
- GRP75敲击减少了ER/线粒体Ca2+,改善了心肌细胞超结构,并减少了亡.
- Knockdown 增加了 ER-线粒体接触点,减少了线粒体相关的 ER 膜 (MAM) 形成,并影响了转移酶和 IP3R 途径.
结论:
- 通过IP3R1-GRP75-VDAC1复合体,GRP75对Ca2+稳态和心肌细胞适应ER压力至关重要.
- 调节GRP75提供了一种潜在的治疗策略,通过调节Ca2+动态和减少亡来治疗心脏中风后的心脏恢复.
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