糖尿病心房中的ROS通过NF-κB信号通路调节阿特罗金-1的SK2降解
Jian Xu1, Dong Zhang2, Yibo Ma2
1Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, China.
The Journal of biological chemistry
|February 9, 2024
概括
糖尿病 (DM) 增加了心房的风险. 这项研究揭示了活性氧物种 (ROS) 和NF-κB信号驱动Atrogin-1表达,导致糖尿病小鼠心中的SK2降解.
科学领域:
- 心脏病学 心脏病学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 糖尿病 (DM) 是心房动 (AF) 的重要危险因素.
- 连接DM与AF的分子机制,特别是关于阿特罗金-1介导的SK2降解,仍然不太清楚.
- 研究反应性氧物种 (ROS),NF-κB信号传递和糖尿病心脏中的Atrogin-1的相互作用至关重要.
研究的目的:
- 阐明ROS,NF-κB信号传递和ADROGIN-1蛋白表达在DM小鼠心房肌肉中的关系.
- 了解这些因素在糖尿病心房肌病中SK2下调中的作用.
- 评估黄素在调节这些途径方面的治疗潜力.
主要方法:
- 采用了链毒素诱导的糖尿病小鼠模型和HL-1细胞培养.
- 评估了SK2表达,ROS生成和NF-κB信号激活.
- 采用H2O2和高葡萄糖治疗,ROS抑制 (二乙烯化),NF-κB沉默 (siRNA) 和染色体免疫沉试验.
- 研究了黄素对DM小鼠Atrogin-1和SK2表达的治疗作用.
主要成果:
- 糖尿病小鼠表现出SK2表达减少,ROS增加,并在心房心肌细胞中激活NF-κB信号.
- 高葡萄糖和H2O2在HL-1细胞中模仿了这些效应.
- 抑制ROS或NF-κB降低了NF-κB和阿特罗金-1,同时在高葡萄糖条件下增加了SK2.
- NF-κB/p65直接与FBXO32 (Atrogin-1) 促进体结合,调节其转录.
- 在DM小鼠中,黄素治疗抑制了Atrogin-1并保持了SK2的表达.
结论:
- ROS/NF-κB信号通路与DM小鼠心房中阿特罗金-1介导的SK2调节有关.
- 这一途径有助于糖尿病中心房功能障碍的发病.
- 针对ROS/NF-κB/Atrogin-1轴,可能使用诸如黄素之类的药物,可能为糖尿病心房并发症提供治疗策略.
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