miR-19-3p/GRSF1/COX1 轴通过维持蛛网膜下腔出血后的线粒体功能减轻早期脑损伤

IF 4.4 1区 医学 Q1 CLINICAL NEUROLOGY Stroke and Vascular Neurology Pub Date : 2024-09-11 DOI:10.1136/svn-2024-003099
Ge Gao, Xiaoyu Sun, Jiajia Xu, Jian Yu, Yang Wang
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The GRSF1 level was downregulated or upregulated by treating the rats and neurons with lentivirus- GRSF1 shRNA (Lenti- GRSF1 shRNA) or lentivirus- GRSF1 (Lenti- GRSF1 ). Results The miR-19-3 p level was upregulated and the protein levels of GRSF1 and COX1 were both downregulated in SAH brain tissue. GRSF1 silence decreased and GRSF1 overexpression increased the protein levels of GRSF1 and COX1 in primary neurons and brain tissue, respectively. Lenti- GRSF1 shRNA aggravated, but Lenti- GRSF1 alleviated, the indicators of neuronal injury and neurological impairment in both in vitro and in vivo SAH conditions. In addition, miR-19-3 p mimic reduced the protein levels of GRSF1 and COX1 in cultured neurons while miR-19-3 p inhibitor increased them. More importantly, Lenti- GRSF1 significantly relieved mitochondrial damage of neurons exposed to OxyHb or induced by SAH and was beneficial to maintaining mitochondrial integrity. 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引用次数: 0

摘要

背景富含鸟嘌呤的 RNA 序列结合因子 1(GRSF1)是一种 RNA 结合蛋白,它最终定位于线粒体并促进细胞色素 C 氧化酶 1(COX1)mRNA 的翻译。然而,miR-19-3 p/GRSF1/COX1 轴的作用尚未在实验性蛛网膜下腔出血(SAH)模型中进行研究。因此,我们研究了 miR-19-3 p/GRSF1/COX1 轴在 SAH 诱导的早期脑损伤(EBI)过程中的作用。方法 用氧血红蛋白(OxyHb)处理原始神经元以模拟体外 SAH。将自体动脉血注入视神经驰管,建立大鼠 SAH 模型。用慢病毒-GRSF1 shRNA(Lenti- GRSF1 shRNA)或慢病毒-GRSF1(Lenti- GRSF1 )处理大鼠和神经元,下调或上调GRSF1水平。结果 SAH 脑组织中 miR-19-3 p 水平上调,GRSF1 和 COX1 蛋白水平下调。在原代神经元和脑组织中,GRSF1沉默会降低GRSF1和COX1的蛋白水平,而GRSF1过表达则会提高GRSF1和COX1的蛋白水平。Lenti- GRSF1 shRNA 会加重体外和体内 SAH 条件下神经元损伤和神经功能损害的指标,而 Lenti- GRSF1 则会减轻神经元损伤和神经功能损害的指标。此外,miR-19-3 p 模拟物降低了培养神经元中 GRSF1 和 COX1 的蛋白水平,而 miR-19-3 p 抑制剂则提高了它们的蛋白水平。更重要的是,Lenti-GRSF1 能明显缓解暴露于 OxyHb 或 SAH 诱导的神经元线粒体损伤,有利于维持线粒体的完整性。相反,Lenti-GRSF1 shRNA 处理会加重神经元线粒体损伤。结论 miR-19-3 p/GRSF1/COX1 轴可能是通过维持线粒体完整性来抑制 SAH 诱导的 EBI 的潜在靶点。如有合理要求,可提供相关数据。
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miR-19-3p/GRSF1/COX1 axis attenuates early brain injury via maintaining mitochondrial function after subarachnoid haemorrhage
Background Guanine-rich RNA sequence binding factor 1 (GRSF1) is an RNA-binding protein, which is eventually localised to mitochondria and promotes the translation of cytochrome C oxidase 1 (COX1) mRNA. However, the role of the miR-19-3 p/GRSF1/COX1 axis has not been investigated in an experimental subarachnoid haemorrhage (SAH) model. Thus, we investigated the role of the miR-19-3 p/GRSF1/COX1 axis in a SAH-induced early brain injury (EBI) course. Methods Primary neurons were treated with oxyhaemoglobin (OxyHb) to simulate in vitro SAH. The rat SAH model was established by injecting autologous arterial blood into the optic chiasma cisterna. The GRSF1 level was downregulated or upregulated by treating the rats and neurons with lentivirus- GRSF1 shRNA (Lenti- GRSF1 shRNA) or lentivirus- GRSF1 (Lenti- GRSF1 ). Results The miR-19-3 p level was upregulated and the protein levels of GRSF1 and COX1 were both downregulated in SAH brain tissue. GRSF1 silence decreased and GRSF1 overexpression increased the protein levels of GRSF1 and COX1 in primary neurons and brain tissue, respectively. Lenti- GRSF1 shRNA aggravated, but Lenti- GRSF1 alleviated, the indicators of neuronal injury and neurological impairment in both in vitro and in vivo SAH conditions. In addition, miR-19-3 p mimic reduced the protein levels of GRSF1 and COX1 in cultured neurons while miR-19-3 p inhibitor increased them. More importantly, Lenti- GRSF1 significantly relieved mitochondrial damage of neurons exposed to OxyHb or induced by SAH and was beneficial to maintaining mitochondrial integrity. Lenti- GRSF1 shRNA treatment, conversely, aggravated mitochondrial damage in neurons. Conclusion The miR-19-3 p/GRSF1/COX1 axis may serve as an underlying target for inhibiting SAH-induced EBI by maintaining mitochondrial integrity. Data are available on reasonable request.
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来源期刊
Stroke and Vascular Neurology
Stroke and Vascular Neurology Medicine-Cardiology and Cardiovascular Medicine
CiteScore
11.20
自引率
1.70%
发文量
63
审稿时长
15 weeks
期刊介绍: Stroke and Vascular Neurology (SVN) is the official journal of the Chinese Stroke Association. Supported by a team of renowned Editors, and fully Open Access, the journal encourages debate on controversial techniques, issues on health policy and social medicine.
期刊最新文献
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