Molecular mechanism of METTL3 regulating hippocampal neuronal injury induced by sepsis-associated encephalopathy.

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry Pub Date : 2025-03-02 DOI:10.1080/13813455.2025.2465337

Qian Zhang, Yan Huo, Runying Zhu, Xujie Zhang, Lingwei Zeng, Zhenjie Hu

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Abstract

Objective: This study explores the mechanism of methyltransferase like 3 (METTL3) on sepsis-associated encephalopathy (SAE)-induced hippocampal neuronal injury.

Methods: A murine model of SAE was established by caecal ligation and puncture. Hippocampal cells were induced by lipopolysaccharide (LPS). The mouse survival was observed and behavioural tests evaluated cognitive function. METTL3 and glutamic-oxaloacetic transaminase 1 (GOT1) expressions were detected via RT-qPCR and Western blot. Immunofluorescence staining examined the co-localization of NeuN and METTL3. The m6A enrichment on GOT1 was determined by MeRIP.

Results: METTL3 and GOT1 were highly expressed in SAE mice and LPS-stimulated hippocampal cells. SAE mice exhibited cognitive function impairment, reduced survival rate, and decreased neuronal cells. LPS induction increased hippocampal cell apoptosis and enhanced inflammation. Silence of METTL3 reduced hippocampal neuronal injury in SAE mice and LPS-induced hippocampal cell injury.

Conclusion: METTL3-mediated m6A modification on GOT1 mRNA elevates GOT1 expression, thereby aggravating SAE-induced hippocampal neuronal injury.

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METTL3调节败血症相关脑病海马神经元损伤的分子机制。

目的：探讨甲基转移酶样3 （METTL3）在脓毒症相关脑病（SAE）诱导的海马神经元损伤中的作用机制。方法：采用结扎法和穿刺法建立小鼠SAE模型。脂多糖（LPS）诱导海马细胞。观察小鼠的存活率，并通过行为测试评估认知功能。RT-qPCR和Western blot检测METTL3和谷草转氨酶1 （GOT1）的表达。免疫荧光染色检测NeuN和METTL3的共定位。m6A在GOT1上的富集用MeRIP测定。结果：METTL3和GOT1在SAE小鼠和lps刺激的海马细胞中高表达。SAE小鼠表现出认知功能障碍、存活率降低和神经元细胞减少。LPS诱导海马细胞凋亡增加，炎症增强。METTL3沉默可减轻SAE小鼠海马神经元损伤和lps诱导的海马细胞损伤。结论：mettl3介导m6A修饰GOT1 mRNA使GOT1表达升高，加重了sae诱导的海马神经元损伤。

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

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.