板素1针对线粒细胞衰变来调节缺血/再输血损伤
Lianjiu Su1,2,3, Jiahao Zhang4, Jing Wang4,5
1Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. sulianjiu@whu.edu.cn.
Communications biology
|August 29, 2023
概括
板素1 (PANX1) 通过抑制线粒细胞吸收 (mitophagy) 来加剧急性损伤 (AKI),这是清除受损线粒体的关键过程. 阻断PANX1可能会保护脏免受缺血/再输液损伤.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 缺血/流 (I/R) 损伤是急性损伤 (AKI) 的主要原因之一.
- 线粒体损伤和 mitoophagy 损伤对 AKI 病原发生有显著的贡献.
- 泛素1 (PANX1) 在I/R损伤期间与炎症和ATP释放有关,但其在AKI中对髓细胞调节的作用尚不清楚.
研究的目的:
- 为了研究板素1 (PANX1) 在调节缺血/回流 (I/R) 损伤期间细胞衰变中的作用.
- 确定PANX1是否是AKI的潜在生物标志物或治疗标.
主要方法:
- 血清PANX1水平测量在心脏手术后AKI患者.
- 我们使用了I/R损伤的小鼠模型和基于细胞的低氧/低氧化 (H/R) 模型.
- 用PANX1的遗传删除来评估其保护作用.
主要成果:
- 血清PANX1水平升高与AKI严重程度相关 (肌素和尿素).
- 遗传PANX1缺失减弱了脏管状细胞死亡,氧化应激以及I/R损伤中的线粒体损伤.
- 发现PANX1通过ATP-P2Y-mTOR信号通路破坏了线粒.
结论:
- PANX1通过抑制线粒细胞衰变,在I/R损伤中起着有害的作用.
- PANX1可以作为一个有价值的生物标志物来预测AKI的发展.
- 向PANX1为缓解与I/R损伤相关的AKI提供了潜在的治疗策略.
更多相关视频
08:40Visualization of Endogenous Mitophagy Complexes In Situ in Human Pancreatic Beta Cells Utilizing Proximity Ligation Assay
Published on: May 2, 2019
5.9K
07:40Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
Published on: May 26, 2023
1.2K
相关概念视频
Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
Electron Transport Chain: Complex I and II
14.5K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
14.5K
Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
