毛蕊花苷通过调控METTL14/CHAC1/NRF2/SLC7A11/GPX4通路抑制OGD/ r诱导的SK-N-SH细胞损伤。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-09-09 DOI:10.1016/j.brainresbull.2025.111543

Liwei Wen , Cheng Zhang , Xia Zhou , Jiaxing Feng , Qiang Li , Fubing Yang

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引用次数: 0

摘要

背景：毛蕊花糖苷（VB）在包括脑出血在内的多种疾病中的潜在治疗价值已被报道。在本研究中，我们旨在探讨VB在缺血性脑卒中中的潜在机制。方法：采用氧葡萄糖剥夺/再氧合（OGD/R）模型建立体外缺血性脑卒中模型。CCK-8法和EdU法检测细胞增殖情况。采用流式细胞术分析细胞凋亡情况。使用ELISA试剂盒估计炎症因子浓度。使用指定的商用试剂盒检测与铁中毒相关的标记物。采用MeRIP法、RIP法和放线菌素D法分析METTL14、CHAC1与IGF2BP2的关系。采用qRT-PCR和western blot检测基因表达。结果：VB促进OGD/ r处理的SK-N-SH细胞增殖，抑制细胞凋亡、炎症和铁凋亡。VB降低OGD/ r处理的SK-N-SH细胞中METTL14的表达，METTL14敲低可减轻OGD/ r诱导的SK-N-SH细胞损伤。METTL14和IGF2BP2介导CHAC1的m6A修饰。CHAC1过表达消除了METTL14敲低对OGD/ r诱导的SK-N-SH细胞损伤的影响。此外，VB对OGD/ r处理的SK-N-SH细胞增殖、凋亡、炎症和铁凋亡的影响可以通过升高METTL14或CHAC1来减弱。此外，VB降低OGD/ r处理的SK-N-SH细胞中NRF2、SLC7A11和GPX4的水平，而METTL14或CHAC1过表达逆转了这一作用。结论：VB通过调控METTL14/CHAC1/NRF2/SLC7A11/GPX4通路促进OGD/ r处理的SK-N-SH细胞增殖，抑制细胞凋亡、炎症和铁凋亡。

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Verbascoside inhibits OGD/R-induced SK-N-SH cell injury by regulating METTL14/CHAC1/NRF2/SLC7A11/GPX4 pathway

Background

The potential therapeutic value of verbascoside (VB) has been reported in a variety of diseases, including cerebral hemorrhage. In this study, we aimed to explore the underlying mechanism of VB in cerebral ischemic stroke.

Methods

The in vitro ischemic stroke model was established by Oxygen-glucose deprivation/reoxygenation (OGD/R) model. CCK-8 assay and EdU assay were performed for cell proliferation. Flow cytometry analysis was adopted to analyze cell apoptosis. ELISA kits were used to estimate the concentrations of inflammatory factors. Ferroptosis-related markers were examined with indicated commercial kits. The relations of METTL14, CHAC1 and IGF2BP2 were analyzed by MeRIP assay, RIP assay and Actinomycin D assay. Gene expression was determined by qRT-PCR and western blot.

Results

VB promoted the proliferation and inhibited apoptosis, inflammation and ferroptosis in OGD/R-treated SK-N-SH cells. VB decreased METTL14 expression in OGD/R-treated SK-N-SH cells and METTL14 knockdown alleviated OGD/R-induced injury of SK-N-SH cells. METTL14 and IGF2BP2 mediates m6A modification of CHAC1. CHAC1 overexpression abrogated the effects of METTL14 knockdown on OGD/R-induced SK-N-SH cell injury. Moreover, the effects of VB on OGD/R-treated SK-N-SH cell proliferation, apoptosis, inflammation and ferroptosis were abated by elevating METTL14 or CHAC1. Besides, VB reduced the levels of NRF2, SLC7A11 and GPX4 in OGD/R-treated SK-N-SH cells, while METTL14 or CHAC1 overexpression reversed the effects.

Conclusion

VB promoted the proliferation and inhibited apoptosis, inflammation and ferroptosis in OGD/R-treated SK-N-SH cells by regulating METTL14/CHAC1/NRF2/SLC7A11/GPX4 pathway.

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.