抑制CTR1表达通过阻断cuproptosis改善低氧/低氧化诱导的肌细胞损伤
Dong-Ge Fu1, Jing-Zi He1, Qi-Chen Mu2
1Physical Education Institute, Yan'an University, Yan'an, 716000, Shaanxi, China; Physical Education Institute, Henan University, Kaifeng, 475000, Henan, China.
Biochemical and biophysical research communications
|October 17, 2024
概括
铜诱导的细胞死亡 (cuproptosis) 促进骨肌肉损伤. 低氧/低氧化增强了这一过程,通过铜载体1 (CTR1) 增加铜的吸收,揭示了一个新的损伤机制.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 病理学 病理学 病理学
背景情况:
- 骨肌肉缺血-反损伤 (IRI) 是一种具有复杂病理的严重疾病.
- 铜,一种依赖铜的细胞死亡途径,与各种细胞功能障碍有关.
研究的目的:
- 为了调查cuproptosis在骨肌肉缺血-再输液损伤 (IRI) 中的作用.
- 阐明缺氧/再氧化 (H/R) 影响肌细胞活力和损伤的机制.
主要方法:
- 研究铜化物 (CuCl2) 对肌细胞活力和细胞内铜水平的影响.
- 分析了铜载体1 (CTR1) 的表达及其在铜吸收中的作用.
- 研究了cuproptosis诱导和抑制对细胞ATP,谷氨,线粒体功能和损伤标志物的影响.
- 研究了H/R对CTR1表达,细胞内铜和肌细胞亡途径激活的作用.
主要成果:
- CuCl2以剂量依赖的方式抑制了肌细胞活力,增加了细胞内铜,并降低了CTR1.1.
- CTR1上调增强了铜的吸收,导致以DLAT寡合化和减少脂质化蛋白质为特征的铜亡.
- Cuproptosis诱导 (elesclomol + CuCl2) 降低了ATP和GSH,降低了线粒体复合体I / III活性,并增加了乳酸盐,MDA,CK和LDH.
- 经过TTM治疗,抑制了cuproptosis,显著恢复了肌细胞损伤.
- H/R诱导了CTR1的表达,增加了细胞内铜和cuproptosis标记物,同时降低了ATP,GSH和线粒体活动.
- 降低CTR1改善了H/R诱导的肌细胞损伤,炎症和cuproptosis激活.
结论:
- Cuproptosis促进了肌细胞细胞损伤.
- H/R通过诱导CTR1表达来增强铜的吸收,从而激活cuproptosis并导致细胞损伤.
- cuproptosis代表了一种新的机制,它是H/R诱导的骨肌损伤的基础.
更多相关视频
07:40Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
Published on: May 26, 2023
1.1K
07:14A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
14.2K
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
02:34Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
01:30The Electron Transport Chain
16.2K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.2K
01:52Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K