尼古丁胺胺 рибоoside 向线粒体展开的蛋白质反应,以减少库普弗细胞中酒精诱导的损伤
Jaeeun Lee1, Hayoung Woo1, Hyunju Kang1,2
1Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA.
The Journal of pathology
|December 3, 2024
概括
尼古丁胺胺 рибоoside (NR) 通过减少库弗弗细胞中的炎症和线粒体功能障碍来缓解与酒精有关的肝损伤. 它调节了激活转录因子5 (ATF5) 依存的线粒体未折叠蛋白反应 (UPR) 途径,表明NR是ALD的潜在治疗方法.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 与酒精有关的肝病 (ALD) 的发病包括线粒体功能障碍和能量代谢受损.
- 库弗尔细胞,肝脏巨细胞,是乙醇诱导的炎症和氧化应激的核心.
- 线粒体展开蛋白反应 (UPRmt) 是对线粒体损伤的关键防御机制.
研究的目的:
- 研究乙醇对库普弗细胞线粒体功能和UPRmt通路的影响.
- 为了确定尼古丁胺 рибоoside (NR) 是否可以减轻乙醇诱导的细胞损伤.
- 阐明激活转录因子5 (ATF5) 在乙醇诱导的UPRmt中的作用.
主要方法:
- 对老鼠永生库弗弗细胞 (ImKCs) 和初级KCs暴露于乙醇.
- 评估炎症,氧化应激和线粒体形态.
- 对UPRmt基因表达和ATF5局部化的分析.
- 在暴露于酒精的肝脏组织中确认UPRmt诱导.
主要成果:
- 乙醇暴露诱导了ImKCs的炎症,氧化应激和线粒体功能障碍.
- NR治疗抵消了乙醇的有害影响,包括UPRmt基因诱导.
- 乙醇增加了ATF5核转位,这是NR抑制的过程.
- 抑制ATF5抑制了乙醇诱导的UPRmt基因表达,证实了ATF5的作用.
结论:
- NR有效地缓解乙醇诱导的氧化应激,炎症和Kupffer细胞中的线粒体功能障碍.
- NR的保护作用部分通过调节ATF5依赖的UPR路径来调节.
- 作为与酒精有关的肝脏疾病的治疗剂,NR显示出希望.
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