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同型半胱氨酸通过下调 pCAMK2A 抑制脑出血后神经突生长的恢复。

Homocysteine impedes neurite outgrowth recovery after intracerebral haemorrhage by downregulating pCAMK2A.

机构信息

Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China.

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Stroke Vasc Neurol. 2023 Aug;8(4):335-348. doi: 10.1136/svn-2022-002165. Epub 2023 Feb 28.

DOI:10.1136/svn-2022-002165
PMID:36854487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10512087/
Abstract

Hyperhomocysteinemia (HHcy) is independently associated with poorer long-term prognosis in patients with intracerebral haemorrhage (ICH); however, the effect and mechanisms of HHcy on ICH are still unclear. Here, we evaluated neurite outgrowth and neurological functional recovery using simulated models of ICH with HHcy in vitro and in vivo. We found that the neurite outgrowth velocity and motor functional recovery in the ICH plus HHcy group were significantly slower than that in the control group, indicating that homocysteine (Hcy) significantly impedes the neurite outgrowth recovery after ICH. Furthermore, phosphoproteomic data and signalome analysis of perihematomal brain tissues suggested that calmodulin-dependent protein kinases 2 (CAMK2A) kinase substrate pairs were significantly downregulated in ICH with HHcy compared with autologous blood injection only, both western blot and immunofluorescence staining confirmed this finding. Additionally, upregulation of pCAMK2A significantly increased neurite outgrowth recovery in ICH with HHcy. Collectively, we clarify the mechanism of HHcy-hindered neurite outgrowth recovery, and pCAMK2A may serve as a therapeutic strategy for promoting neurological recovery after ICH.

摘要

高同型半胱氨酸血症（HHcy）与脑出血（ICH）患者的长期预后较差独立相关；然而，HHcy 对 ICH 的影响和机制仍不清楚。在这里，我们通过体外和体内模拟 HHcy 存在的 ICH 模型来评估神经突生长和神经功能恢复。我们发现，ICH 加 HHcy 组的神经突生长速度和运动功能恢复明显慢于对照组，表明同型半胱氨酸（Hcy）显著阻碍 ICH 后神经突生长的恢复。此外，对血肿周围脑组织的磷酸蛋白质组学数据和信号组分析表明，与仅自体血注射相比，HHcy 存在的 ICH 中钙调蛋白依赖性蛋白激酶 2（CAMK2A）激酶底物对明显下调，Western blot 和免疫荧光染色均证实了这一发现。此外，pCAMK2A 的上调显著增加了 HHcy 存在的 ICH 中的神经突生长恢复。总之，我们阐明了 HHcy 阻碍神经突生长恢复的机制，pCAMK2A 可能成为促进 ICH 后神经功能恢复的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/a90482028ef4/svn-2022-002165f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/a368f48887fc/svn-2022-002165f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/ff54dff3af69/svn-2022-002165f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/76f55a4e97fa/svn-2022-002165f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/d37a5e75de33/svn-2022-002165f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/a90482028ef4/svn-2022-002165f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/a368f48887fc/svn-2022-002165f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/ff54dff3af69/svn-2022-002165f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/76f55a4e97fa/svn-2022-002165f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/d37a5e75de33/svn-2022-002165f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7430/10512087/a90482028ef4/svn-2022-002165f05.jpg

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本文引用的文献

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