缺血后条件调节脑卒中新的细胞死亡机制:二硫化血症

IF 4.8 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biomolecules Pub Date : 2024-10-31 DOI:10.3390/biom14111390
Shanpeng Liu, Qike Wu, Can Xu, Liping Wang, Jialing Wang, Cuiying Liu, Heng Zhao
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引用次数: 0

摘要

背景和目的:脑卒中是一个严重的健康问题,但却没有有效的神经保护措施。我们探讨了缺血后条件(IPostC)减轻中风诱发的脑损伤的潜力,重点是它与二硫化硫的相互作用,二硫化硫是一种以蛋白质二硫化物积累为特征的新型细胞死亡途径。我们旨在通过基因测序和小鼠实验分析,阐明 IPostC 对中风的保护机制:通过初步调查,我们确定了 27 个二硫化相关基因(DRGs),并发现了它们之间的相互作用。此外,差异基因分析还发现了 11 个与二硫化硫、中风和 IPostC 相关的潜在候选基因。我们的综合研究采用了多种分析方法,包括机器学习、功能富集分析、免疫分析、药物敏感性分析和 qPCR 实验,以深入了解这些过程的分子机制:我们的研究确定并扩展了对中风至关重要的二硫化相关基因(DRGs)列表,揭示了关键基因及其相互作用。通过生物信息学分析(包括 PCA、UMAP 和差异基因表达),我们能够区分中风的影响和后处理的影响,并确定过氧化物酶 1 (PRDX1) 为关键的相关基因。GSEA 强调了 PRDX1 参与缺血性损伤的保护性通路,而它与各种蛋白的相关性则表明它对中风病理有着广泛的影响。通过构建 ceRNA 网络和分析药物敏感性,我们探索了 PRDX1 的调控机制,并提出了新的治疗途径。此外,我们的免疫浸润分析将 PRDX1 与关键免疫细胞联系起来,强调了它在中风进展和恢复中的双重作用。基于共定位分析,PRDX1 被确定为缺血性中风的关键靶点,该分析揭示了 PRDX1 和缺血性中风共享因果变异 rs17522918。PRDX1相关甲基化位点(cg02631906和cg08483560)与缺血性中风风险之间的因果关系进一步验证了PRDX1是一个关键靶点:这些结果表明,DRGs 与各种细胞死亡途径和免疫过程相互关联,可能有助于 IPostC 调节中风的细胞死亡机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ischemic Postconditioning Regulates New Cell Death Mechanisms in Stroke: Disulfidptosis.

Background and objective: Stroke poses a critical health issue without effective neuroprotection. We explore ischemic postconditioning's (IPostC) potential to mitigate stroke-induced brain injury, focusing on its interaction with disulfidptosis, a novel cell death pathway marked by protein disulfide accumulation. We aim to clarify IPostC's protective mechanisms against stroke through gene sequencing and experimental analysis in mice.

Methods: Through our initial investigation, we identified 27 disulfidptosis-related genes (DRGs) and uncovered their interactions. Additionally, differential gene analysis revealed 11 potential candidate genes that are linked to disulfidptosis, stroke, and IPostC. Our comprehensive study employed various analytical approaches, including machine learning, functional enrichment analysis, immune analysis, drug sensitivity analysis, and qPCR experiments, to gain insights into the molecular mechanisms underlying these processes.

Results: Our study identified and expanded the list of disulfidptosis-related genes (DRGs) critical to stroke, revealing key genes and their interactions. Through bioinformatics analyses, including PCA, UMAP, and differential gene expression, we were able to differentiate the effects of stroke from those of postconditioning, identifying Peroxiredoxin 1 (PRDX1) as a key gene of interest. GSEA highlighted PRDX1's involvement in protective pathways against ischemic damage, while its correlations with various proteins suggest a broad impact on stroke pathology. Constructing a ceRNA network and analyzing drug sensitivities, we explored PRDX1's regulatory mechanisms, proposing novel therapeutic avenues. Additionally, our immune infiltration analysis linked PRDX1 to key immune cells, underscoring its dual role in stroke progression and recovery. PRDX1 is identified as a key target in ischemic stroke based on colocalization analysis, which revealed that PRDX1 and ischemic stroke share the causal variant rs17522918. The causal relationship between PRDX1-related methylation sites (cg02631906 and cg08483560) and the risk of ischemic stroke further validates PRDX1 as a crucial target.

Conclusions: These results suggest that the DRGs are interconnected with various cell death pathways and immune processes, potentially contributing to IPostC regulating cell death mechanisms in stroke.

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来源期刊
Biomolecules
Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
3.60%
发文量
1640
审稿时长
18.28 days
期刊介绍: Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications.  Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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