RBM25通过CHOP相关的内质网膜应激调节缺氧心肌细胞亡
Ziwei Zhu1, Jie Pu1, Yongnan Li2
1Department of Cardiovascular Medicine, Lanzhou University Second Hospital, Lanzhou, 730000, China.
Cell stress & chaperones
|September 22, 2023
概括
RNA结合动机蛋白25 (RBM25) 在缺血性心力衰竭中升高,通过内分泌网膜应激和CHOP通路促进细胞亡. 抑制RBM25可以改善心脏功能,这表明它是治疗点.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 缺血性心力衰竭 (HF) 是全球主要的健康负担.
- 准亡级联为HF提供了一个潜在的治疗策略.
- 目前尚不清楚RNA结合基因蛋白25 (RBM25) 在缺血性肝炎中的作用.
研究的目的:
- 调查RBM25在缺血性高血压病原发生的潜在机制.
- 为了确定RBM25是否会在缺血性条件下影响细胞亡和心脏功能.
主要方法:
- 在心肌细胞中确立的缺血性HF和氧-葡萄糖剥夺 (OGD) 的老鼠模型.
- 评估心脏功能,心脏病发作大小,并使用心声回声学,组织学,ELISA,西部斑点和免疫光学来评估细胞亡.
- 使用ER追踪器观察内分泌网膜 (ER) 形态.
主要成果:
- 在缺氧条件下,RBM25表达在心肌细胞中显著上调,无论是体外还是体外.
- 过度表达RBM25导致心肌细胞亡的增加.
- 经ER压力诱导RBM25上调,通过CHOP通路促进了细胞亡.
- 通过阻断CHOP信号传递,抑制RBM25改善了细胞亡和改善了心脏功能.
结论:
- 在缺血性高血压中,RBM25被上调,并通过ER压力和CHOP通路促进细胞亡,从而导致心脏功能障碍.
- 降低RBM25表达可以逆转细胞亡介导的心脏功能障碍.
- RBM25代表了治疗缺血性心力衰竭的潜在治疗标.
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