MRPL41, as a target for acupuncture, promotes neuron apoptosis in models of ischemic stroke via activating p53 pathway

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-10-13 DOI:10.1016/j.neuint.2024.105881
Hong Guo , Yuanwei Dong , Danqing Luo , Meng Gong , Jianfeng Sun , Zhipeng Wu , Zhixiang Liu , Lei Zhong , Song Jin
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Abstract

Neuronal death is the key cause of ischemic stroke. Acupuncture (Acu) is a recognized method for the treatment and amelioration of cerebral ischemia. However, the molecular mechanism of Acu for treating ischemic stroke has not yet been detailedly elucidated. Based our microarray analysis results, mitochondrial ribosomal protein L41 (MRPL41), which is related to apoptosis, was identified as the target of Acu. MRPL41 expression was increased in middle cerebral artery occlusion/reperfusion (MCAO/R) model and reduced after Acu treatment. Following, MCAO/R model and oxygen and glucose deprivation/reoxygenation (OGD/R) model were established to explore the effect of MRPL41. Knockdown of MRPL41 increased cell viability and ani-apoptotic protein (Bcl-2) expression, and reduced apoptosis intensity and pro-apoptotic protein (Bax and Cleaved caspase-3) of OGD/R neurons. In vivo, MRPL41 silencing decreased neurological severity score, shrank infarct area, reduced encephaledema and neuron apoptosis. In addition, reduction of MRPL41 caused loss of p53. Our data uncover that Acu targets MRPL41, following with inhibiting neuron apoptosis via p53 pathway, thereby ameliorating ischemic stroke.
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作为针灸靶点的MRPL41可通过激活p53通路促进缺血性中风模型中神经元的凋亡。
神经元死亡是缺血性中风的主要原因。针灸(Acupuncture,Acu)是公认的治疗和改善脑缺血的方法。然而,针灸治疗缺血性中风的分子机制尚未得到详细阐明。根据我们的芯片分析结果,与细胞凋亡有关的线粒体核糖体蛋白 L41(MRPL41)被确定为 Acu 的靶点。MRPL41在大脑中动脉闭塞/再灌注(MCAO/R)模型中表达增加,而在Acu治疗后表达减少。随后,建立了MCAO/R模型和氧和葡萄糖剥夺/再氧合(OGD/R)模型来探讨MRPL41的作用。敲除MRPL41增加了OGD/R神经元的细胞活力和抗凋亡蛋白(Bcl-2)的表达,降低了细胞凋亡强度和促凋亡蛋白(Bax和Caspase-3)的表达。在体内,MRPL41沉默可降低神经系统严重程度评分,缩小梗死面积,减轻脑水肿和神经元凋亡。此外,MRPL41的减少会导致p53的缺失。我们的数据发现,Acu以MRPL41为靶点,通过p53通路抑制神经元凋亡,从而改善缺血性中风。
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上海源叶 Poly-l-lysine
来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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