脊髓缺血再灌注损伤诱导神经元铜突。

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lei Xie, Hang Wu, Qiuping He, Weipeng Shi, Xiao Xiao, Tengbo Yu
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引用次数: 0

摘要

背景:脊髓缺血再灌注损伤(SCIRI)是一种严重的疾病,可导致不可逆的神经元损伤,导致感觉和运动功能丧失。铜质增生是一种新的细胞死亡形式,已在多种疾病中得到研究。然而,铜突起在SCIRI中的作用和机制仍有待阐明。结果:转录组分析结果显示,调控铜离子外排的ATP7B显著下调。同时,另一个关键的铜形体相关基因FDX1也发生了显著改变。因此,我们在体内和体外进行了qPCR和Western blot检测铜裂相关基因的变化。结果表明,SCIRI或OGD/R确实激活了铜突起。此外,免疫荧光/免疫组织化学染色和神经元活性测试与上述结果一致。此外,我们还证明了铜螯合剂和铜还原抑制剂四硫钼酸铵不仅可以改善神经元损伤和促进神经元存活,还可以改善下肢运动功能障碍。结论:SCIRI引起ATP7B下调,阻断铜离子外排,导致铜离子积累、DLAT寡聚、铁硫簇蛋白降解,最终导致神经元铜突起。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Spinal cord ischemia reperfusion injury induces cuproptosis in neurons.

Background: Spinal cord ischemia reperfusion injury (SCIRI) is a serious disease that can result in irreversible neuronal damage, leading to the loss of sensory and motor function. Cuproptosis, a novel form of regulated cell death, has been studied in various diseases. However, the role and mechanism of cuproptosis in SCIRI remain to be elucidated.

Results: The results of transcriptome analysis showed significant downregulation of ATP7B, which regulates copper ion efflux. Concurrently, another key cuproptosis-related gene, FDX1, was significantly altered. Thus, we performed qPCR and Western blot assays in vivo and in vitro to detect changes in cuproptosis-related genes. The results indicated that cuproptosis was indeed activated by SCIRI or OGD/R. Moreover, immunofluorescence/immunohistochemitry staining and neuronal activity tests were consistent with the above results. Furthermore, we also proved that ammonium tetrathiomolybdate, a copper chelator and cuproptosis inhibitor, could not only ameliorate neuronal damage and promote neuronal survival but also improve lower limb motor dysfunction.

Conclusions: SCIRI caused ATP7B downregulation, which blocked copper ion efflux, leading to copper ion accumulation, DLAT oligomerization, degradation of iron-sulfur cluster proteins and ultimately cuproptosis in neurons.

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来源期刊
Cell and Bioscience
Cell and Bioscience BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
10.70
自引率
0.00%
发文量
187
审稿时长
>12 weeks
期刊介绍: Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
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