DNA2 knockout aggravates cerebral ischemia/reperfusion injury by reducing postsynaptic Homer1a.

IF 4 1区 生物学 Q1 ZOOLOGY Zoological Research Pub Date : 2025-01-18 DOI:10.24272/j.issn.2095-8137.2024.269
Ting Ma, Yu-Meng Li, Peng-Yu Ren, Shi-Quan Wang, Xiang-Long Liu, Wen-Bo Lv, Wu-Gang Hou, Wen-Qiang Zuo, Wei-Qiang Lin, Jian Sima, An-Qi Geng
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引用次数: 0

Abstract

DNA2, a multifunctional enzyme with structure-specific nuclease, 5 '-to-3 ' helicase, and DNA-dependent ATPase activities, plays a pivotal role in the cellular response to DNA damage. However, its involvement in cerebral ischemia/reperfusion (I/R) injury remains to be elucidated. This study investigated the involvement of DNA2 in cerebral I/R injury using conditional knockout (cKO) mice ( Nestin-Cre) subjected to middle cerebral artery occlusion (MCAO), an established model of cerebral I/R. Results demonstrated a gradual up-regulation of DNA2 expression, peaking at 72 h post-MCAO. Notably, DNA2 cKO mice exhibited more pronounced brain injury, neurological deficits, and neuronal apoptosis within the penumbra following MCAO. Additionally, DNA2 expression was elevated in an oxygen-glucose deprivation/reoxygenation (OGD/R) cell culture model, and DNA2 knockdown (KD) exacerbated neuronal apoptosis and oxidative stress. Transcriptome analysis of ischemic penumbra tissues via RNA sequencing revealed significant down-regulation of Homer1 in DNA2 cKO mice. Furthermore, in vitro experiments demonstrated that overexpression of Homer1a ameliorated DNA2 KD-induced neuronal apoptosis. Collectively, these findings demonstrate that DNA2 deficiency exacerbates cerebral I/R injury through the down-regulation of Homer1a, highlighting a novel regulatory axis in ischemic neuroprotection.

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来源期刊
Zoological Research
Zoological Research Medicine-General Medicine
CiteScore
7.60
自引率
10.20%
发文量
1937
审稿时长
8 weeks
期刊介绍: Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.
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