SERP1 Alleviates Cerebral Ischemia/Reperfusion Injury by Inhibiting ER Stress-Mediated Apoptosis

IF 3.1 3区生物学 Q3 CELL BIOLOGY

Cell Biology International Pub Date : 2025-05-02 DOI:10.1002/cbin.70029

Le Yin, Dan Wang, Xinyue Zhang, Xiao Wang, Hong Jiao, Xiaodan Liu, Jiaolin Zheng

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Abstract

Ischemic stroke is a common disease of the central nervous system, and endoplasmic reticulum (ER) stress-induced apoptosis plays a key role in brain damage following ischemic stroke. Stress-associated endoplasmic reticulum protein 1 (SERP1) is a Sec. 61-associated polypeptide induced by ER stress, which is implicated in stabilizing membrane proteins during ER stress. However, the precise molecular mechanism of SERP1 in ischemic stroke is still unknown. This study aimed to explore the protective effect of SERP1 against cerebral ischemia/reperfusion (I/R) injury. Male Sprague-Dawley rats with transient middle cerebral artery occlusion/reperfusion (tMCAO/R) were used to simulate cerebral I/R injury in vivo. To mimic the cerebral I/R injury in vitro, PC12 cells were treated with oxygen glucose deprivation/reperfusion (OGD/R). The results revealed that the SERP1 expression was increased during cerebral I/R injury in vivo and in vitro. SERP1 knockdown promoted apoptosis and ER stress as well as aggravated I/R-induced brain injury in rats with tMCAO/R, but SERP1 overexpression presented the opposite effects. SERP1 also alleviated OGD/R-induced cell damage in PC12 cells. Mechanically, SERP1 inhibited the ER stress-induced neuronal apoptosis through the PERK-EIF2α-ATF4-CHOP pathway. In conclusion, these results suggest that SERP1 may be a novel candidate gene for therapies against cerebral I/R injury.

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SERP1通过抑制内质网应激介导的细胞凋亡减轻脑缺血再灌注损伤。

缺血性脑卒中是一种常见的中枢神经系统疾病，内质网应激诱导的细胞凋亡在缺血性脑卒中后的脑损伤中起关键作用。应激相关内质网蛋白1 （SERP1）是内质网应激诱导的61节相关多肽，参与内质网应激期间膜蛋白的稳定。然而，SERP1在缺血性卒中中的确切分子机制尚不清楚。本研究旨在探讨SERP1对脑缺血再灌注（I/R）损伤的保护作用。采用雄性Sprague-Dawley大鼠短暂性大脑中动脉闭塞/再灌注（tMCAO/R）模型模拟体内脑I/R损伤。为了模拟体外脑I/R损伤，对PC12细胞进行氧葡萄糖剥夺/再灌注（OGD/R）处理。结果显示，在体内和体外脑I/R损伤过程中，SERP1表达升高。SERP1敲低可促进tMCAO/R大鼠的细胞凋亡和内质网应激，加重I/R诱导的脑损伤，而SERP1过表达则相反。SERP1还能减轻OGD/ r诱导的PC12细胞损伤。机制上，SERP1通过PERK-EIF2α-ATF4-CHOP途径抑制内质网应激诱导的神经元凋亡。总之，这些结果表明SERP1可能是治疗脑I/R损伤的一个新的候选基因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Biology International 生物-细胞生物学

CiteScore

7.60

自引率

0.00%

发文量

208

审稿时长

1 months

期刊介绍： Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.