ZNF655-mediated neuroprotection in cerebral ischemia-reperfusion injury via Akt/Nrf2 pathway modulation

IF 3.2 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI:10.1016/j.brainres.2025.150091

Wanyi Wei , Zongkai Wu , Yuehong Yue , Yang Zhang , Hebo Wang

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引用次数: 0

Abstract

Background

Cerebral ischemia–reperfusion injury (CIRI) involves complex pathological processes, including oxidative stress, inflammatory responses, and apoptosis. Zinc finger protein 655 (ZNF655) is implicated in the regulation of the Akt signaling pathway, which in turn activates nuclear factor erythroid 2–related factor 2 (Nrf2) via phosphorylation, enhancing its stability and transcriptional activity. This pathway plays a critical role in mediating antioxidant defenses, suppressing inflammation, and inhibiting apoptosis. This study aimed to explore the potential neuroprotective role of ZNF655 in CIRI through modulation of the Akt/Nrf2 signaling cascade.

Methods

An in vitro model of CIRI was established using SH-SY5Y cells subjected to oxygen-glucose deprivation followed by reoxygenation (OGD/R). Cells were infected with adenoviral vector encoding ZNF655 to upregulate ZNF655 expression. The mRNA levels were measured by real-time quantitative PCR (RT-qPCR). Protein levels were determined by immunoblotting. Cell viability was assessed via cell counting kit-8 (CCK-8) assay. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Oxidative stress was monitored by dichlorofluorescein diacetate (DCFH-DA) probe. Inflammatory cytokine release was detected by enzyme-linked immunosorbent assay (ELISA).

Results

ZNF655 expression was significantly downregulated under OGD/R conditions compared with normoxic controls. Overexpression of ZNF655 markedly attenuated OGD/R-induced cell apoptosis, oxidative stress, and pro-inflammatory cytokine production. ZNF655 promoted Akt phosphorylation, facilitated Nrf2 nuclear translocation, and upregulated expression of downstream antioxidant genes.

Conclusion

Pharmacological inhibition of Akt or silencing of Nrf2 attenuated the neuroprotective effects of ZNF655. These findings indicate that ZNF655 exerts neuroprotective effects against OGD/R-induced injury by activating the Akt/Nrf2 signaling pathway.

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znf655介导的Akt/Nrf2通路在脑缺血再灌注损伤中的神经保护作用。

背景：脑缺血再灌注损伤（CIRI）涉及复杂的病理过程，包括氧化应激、炎症反应和细胞凋亡。锌指蛋白655 （ZNF655）参与调控Akt信号通路，进而通过磷酸化激活核因子红系2相关因子2 (Nrf2)，增强其稳定性和转录活性。该通路在介导抗氧化防御、抑制炎症和抑制细胞凋亡中起关键作用。本研究旨在探讨ZNF655通过调节Akt/Nrf2信号级联在CIRI中的潜在神经保护作用。方法：采用SH-SY5Y细胞缺氧-葡萄糖剥夺-再氧合（OGD/R）法建立CIRI体外模型。用编码ZNF655的腺病毒载体感染细胞，上调ZNF655的表达。采用实时荧光定量PCR （RT-qPCR）检测mRNA水平。免疫印迹法测定蛋白水平。通过细胞计数试剂盒-8 （CCK-8）测定细胞活力。通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）评估细胞凋亡。采用双乙酸二氯荧光素（DCFH-DA）探针监测氧化应激。采用酶联免疫吸附试验（ELISA）检测炎症细胞因子释放。结果：与正常对照相比，OGD/R条件下ZNF655的表达明显下调。过表达ZNF655可显著减弱OGD/ r诱导的细胞凋亡、氧化应激和促炎细胞因子的产生。ZNF655促进Akt磷酸化，促进Nrf2核易位，上调下游抗氧化基因的表达。结论：药理抑制Akt或沉默Nrf2可减弱ZNF655的神经保护作用。这些结果表明，ZNF655通过激活Akt/Nrf2信号通路，对OGD/ r诱导的损伤具有神经保护作用。

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

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.