DJ-1 inhibits ferroptosis in cerebral ischemia-reperfusion via ATF4/HSPA5 pathway

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international Pub Date : 2023-10-10 DOI:10.1016/j.neuint.2023.105628

Yumei Li , Tianyi Chen , Ying Xue , Yuan Wang , Li Peng , Chenglong Wang , Shanshan Yu

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引用次数: 0

Abstract

DJ-1 has been confirmed to have neuroprotective effects. Ferroptosis is an iron-dependent programmed cell death mode associated with ischemic stroke. The ATF4/HSPA5 pathway has been shown to play an important role in the regulation of ferroptosis. To explore the role and possible mechanism of DJ-1 in regulating ferroptosis in cerebral ischemia-reperfusion injury. In this study, Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to simulate cerebral ischemia-reperfusion injury in vivo. Detected ferroptosis-related indicators and observed mitochondrial morphology in brain tissue using transmission electron microscopy. ATF4 was subsequently interfered to observe the effect of DJ-1 on ferroptosis. The results suggest that after interfering with DJ-1, the iron content and malondialdehyde (MDA) content of ferroptosis-related indicators increased, the GSH content decreased, and the mitochondrial structure was severely damaged. We then found that DJ-1 attenuated ferroptosis following ATF4 reduction. In this study, we found that the neuroprotective effect of DJ-1 is related to the inhibition of ferroptosis, and its molecular mechanism is closely related to the ATF4/HSPA5 pathway, which may play a key role in inhibiting brain ischemia-reperfusion (I/R) ferroptosis.

查看原文本刊更多论文

DJ-1通过ATF4/HSPA5途径抑制脑缺血再灌注中的脱铁性贫血。

DJ-1已被证实具有神经保护作用。脱铁症是一种与缺血性中风相关的铁依赖性程序性细胞死亡模式。ATF4/HSPA5通路已被证明在脱铁性贫血的调节中发挥重要作用。探讨DJ-1在脑缺血再灌注损伤中调节铁蛋白脱失的作用及其可能机制。本研究采用大脑中动脉闭塞/再灌注（MCAO/R）模拟脑缺血再灌注损伤。使用透射电子显微镜检测脑组织中脱铁相关指标并观察线粒体形态。随后干扰ATF4以观察DJ-1对脱铁性贫血的影响。结果表明，DJ-1干扰后，脱铁相关指标的铁含量和丙二醛（MDA）含量增加，GSH含量降低，线粒体结构严重受损。然后我们发现DJ-1在ATF4还原后减轻了脱铁性贫血。在本研究中，我们发现DJ-1的神经保护作用与抑制铁蛋白脱失有关，其分子机制与ATF4/HSPA5通路密切相关，后者可能在抑制脑缺血再灌注（I/R）铁蛋白脱脱中发挥关键作用。

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

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.