Ubiquitin-specific peptidase 14 promotes neuron injury by stabilizing acyl-CoA synthetase long-chain family member 4 through deubiquitination.

IF 3.1 4区医学 Q2 PATHOLOGY

Cytojournal Pub Date : 2025-02-05 eCollection Date: 2025-01-01 DOI:10.25259/Cytojournal_52_2024

Xiaoting Hao, Ying Liu

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引用次数: 0

Abstract

Objective: Ubiquitin-specific peptidase 14 (USP14) may be a target for stroke treatment. Our study aims to explore the molecular mechanism of USP14 in the stroke process.

Material and methods: A stroke cell model was constructed using oxygen-glucose deprivation/reoxygenation (OGD/R)-induced SK-N-SH cells, and cell growth was assessed using cell counting kit 8 assay, EdU assay, and flow cytometry. Proinflammatory cytokine levels were tested through an enzyme-linked immunosorbent assay. The levels of USP14 and acyl-CoA synthetase long-chain family member 4 (ACSL4) were determined through Western blot and quantitative real-time polymerase chain reaction, whereas the interaction of USP14 and ACS14 was evaluated by co-immunoprecipitation assay.

Results: OGD/R-induced SK-N-SH cell injury by enhancing ferroptosis and the knockdown of USP14 inhibited OGD/R-induced cell inflammation, apoptosis, and ferroptosis. Moreover, USP14 enhanced ACSL4 protein expression through deubiquitination. ACSL4 silencing mitigated neuron injury, and ACSL4 upregulation abolished USP14 knockdown-mediated inhibition of neuron injury.

Conclusion: USP14 can enhance neuron injury through stabilizing ACSL4 protein expression.

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泛素特异性肽酶14通过去泛素化来稳定酰基辅酶a合成酶长链家族成员4，从而促进神经元损伤。

目的：泛素特异性肽酶14 （USP14）可能是脑卒中治疗的靶点。我们的研究旨在探讨USP14在脑卒中过程中的分子机制。材料和方法：采用氧-葡萄糖剥夺/再氧化（OGD/R）诱导的SK-N-SH细胞构建脑卒中细胞模型，采用细胞计数试剂盒8、EdU、流式细胞术检测细胞生长情况。通过酶联免疫吸附法检测促炎细胞因子水平。采用Western blot和实时定量聚合酶链反应检测USP14与酰基辅酶a合成酶长链家族成员4 （ACSL4）的水平，采用共免疫沉淀法检测USP14与ACS14的相互作用。结果：OGD/ r通过增强铁下垂诱导SK-N-SH细胞损伤，敲低USP14可抑制OGD/ r诱导的细胞炎症、凋亡和铁下垂。此外，USP14通过去泛素化增强ACSL4蛋白的表达。ACSL4沉默可减轻神经元损伤，ACSL4上调可消除USP14敲低介导的神经元损伤抑制。结论：USP14通过稳定ACSL4蛋白表达而增强神经元损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytojournal PATHOLOGY-

CiteScore

2.20

自引率

42.10%

发文量

审稿时长

>12 weeks

期刊介绍： The CytoJournal is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Diagnostic Cytopathology including Molecular aspects. The journal is owned by the Cytopathology Foundation and published by the Scientific Scholar.