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在与酒精有关的肝病中,StARD1的区域表达和氧化应激

Raquel Fucho¹, Estel Solsona-Vilarrasa¹, Sandra Torres¹

¹Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), CSIC, Barcelona, Spain; Liver Unit, Hospital Clinic I Provincial de Barcelona, Barcelona, Spain; Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBEREHD, Madrid, Spain.

Journal of lipid research

|July 20, 2023

概括

类固醇性急性调节性蛋白相关脂质转移 (StARD1) 主要表达在酒精性肝病 (ALD) 期间的周静脉区域. 这种区域表达通过改变线粒体功能和脂质代谢,导致肝损伤.

科学领域:

肝病学肝病学是一种肝病学.
分子生物学分子生物学
生物化学生物化学

背景情况:

与酒精有关的肝病 (ALD) 是慢性肝病的主要原因之一,其致病性尚未完全理解.
酒精诱导的肝损伤显示了肝脏内明显的区域分布.
StARD1与其他慢性肝病有关.

研究的目的:

研究StARD1在酒精性肝病中的作用和区域表达.
在ALD模型中阐明StARD1对肝细胞功能和损伤的影响.

主要方法:

在急性-慢性和慢性ALD的小鼠模型中分析StARD1表达.
在体外研究中,使用暴露于乙醇和化学缺氧的初级小鼠肝细胞.
使用显微镜和生化分析评估线粒体胆固醇,脂质过氧化,糖原和脂质滴.
使用细胞外流量分析评估线粒体呼吸.
产生和分析肝细胞特异的Stard1淘汰赛 (KO) 鼠.

主要成果:

主要在肝脏的周静脉 (PV) 区域发现了StARD1表达,早在饮酒10天后就会出现.
乙醇和缺氧增加了孤立肝细胞中的StARD1表达.
区域性StARD1表达导致线粒体胆固醇积累,并增加PV肝细胞中的脂质过氧化.
酒精养改变了线粒体形态和功能,具有偏好的脂质滴积累和增加了PV区的线粒体数量.
在PV肝细胞中的Stard1KO废除了酒精诱导的损伤标志物.

结论:

在ALD期间,StARD1在肝脏中表现出区域表达,主要在周静脉区域.
通过影响线粒体功能和脂质代谢,StARD1在ALD特征的区域依赖性肝损伤中发挥着关键作用.
在ALD中,周门肝细胞和周静脉肝细胞之间存在不同的线粒体形态和功能.

关键词:

与酒精相关的肝病是与酒精有关的肝病.胆固醇胆固醇胆固醇是一种线粒体中的线粒体.氧化应激是一种氧化应激.

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