Mechanism of HDAC2 regulating Nrf2 acetylation level in neuronal ferroptosis of neonatal rats with hypoxic-ischemic brain injury.

IF 1.5 4区医学 Q4 NEUROSCIENCES

Brain injury Pub Date : 2025-03-10 DOI:10.1080/02699052.2025.2468309

Xin Liu, Xuwei Tao, Zhen Xiong, Huizhen Wang, Linkong Zeng

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引用次数: 0

Abstract

Objective: We investigated the mechanism of histone deacetylase 2 (HDAC2) modulating nuclear factor erythroid 2-related factor 2 (Nrf2) acetylation level in neuronal ferroptosis of hypoxic-ischemic brain injury (HIBI) neonatal rats.

Methods: The pathological damage and neuronal injury in the hippocampal CA1 region of HIBI neonatal rat models were assessed by HE and Nissl staining. Levels of neuron-specific enolase (NSE), glutathione peroxidase 4 (GPX4), HDAC2, Nrf2, glutathione (GSH), reactive oxygen species (ROS), malondialdehyde (MDA), active Fe²⁺, Nrf2 acetylation, and nuclear Nrf2 in hippocampal tissues were determined.

Results: HIBI induced upregulation of HDAC2 expression, causing hippocampal neuronal ferroptosis in neonatal rats, as evidenced by dissolved hippocampal CA1 region, neuronatrophy, reduced number of neurons, abated NSE and GPX4 levels, decreased NeuN+/GPX4+ cells, diminished GSH level, and increased levels of ROS, MDA and active Fe²⁺. Inhibition of HDAC2 partially ameliorated neuronal ferroptosis in HIBI neonatal rats. HDAC2 regulated Nrf2 expression and repressed Nrf2 nuclear translocation by mediating Nrf2 deacetylation. Inhibition of Nrf2 partially reversed the ameliorative effect of HDAC2 on neuronal ferroptosis in HIBI neonatal rats.

Conclusion: HDAC2 modulated neuronal ferroptosis in HIBI neonatal rats by mediating Nrf2 deacetylation.

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HDAC2调控Nrf2乙酰化水平在缺氧缺血性脑损伤新生大鼠神经元铁凋亡中的作用机制

目的：探讨组蛋白去乙酰化酶2 （HDAC2）在缺氧缺血性脑损伤（HIBI）新生大鼠神经元凋亡中调节核因子-红细胞2相关因子- 2 （Nrf2）乙酰化水平的机制。方法：采用HE和Nissl染色观察HIBI新生大鼠模型海马CA1区的病理损伤和神经元损伤情况。测定海马组织中神经元特异性烯醇化酶（NSE）、谷胱甘肽过氧化物酶4 （GPX4）、HDAC2、Nrf2、谷胱甘肽（GSH）、活性氧（ROS）、丙二醛（MDA）、活性铁离子（Fe2+）、Nrf2乙酰化和核Nrf2水平。结果：HIBI诱导HDAC2表达上调，引起新生大鼠海马神经元铁凋亡，表现为海马CA1区溶解，神经元萎缩，神经元数量减少，NSE和GPX4水平降低，NeuN+/GPX4+细胞减少，GSH水平降低，ROS、MDA和活性Fe2+水平升高。抑制HDAC2可部分改善HIBI新生大鼠神经元铁下垂。HDAC2通过介导Nrf2去乙酰化调控Nrf2表达，抑制Nrf2核易位。抑制Nrf2可部分逆转HDAC2对HIBI新生大鼠神经元铁下垂的改善作用。结论：HDAC2通过介导Nrf2去乙酰化调节HIBI新生大鼠神经元铁凋亡。

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来源期刊

Brain injury 医学-康复医学

CiteScore

3.50

自引率

5.30%

发文量

148

审稿时长

12 months

期刊介绍： Brain Injury publishes critical information relating to research and clinical practice, adult and pediatric populations. The journal covers a full range of relevant topics relating to clinical, translational, and basic science research. Manuscripts address emergency and acute medical care, acute and post-acute rehabilitation, family and vocational issues, and long-term supports. Coverage includes assessment and interventions for functional, communication, neurological and psychological disorders.