文章摘要
沙旭栋,鲁 佳,林佳源,黄立栋,马小莉,虞志华.TRPV1介导H4组蛋白乳酸化调控AD炎症激活小胶质细胞[J].,2024,(3):401-404
TRPV1介导H4组蛋白乳酸化调控AD炎症激活小胶质细胞
TRPV1 Regulates Reactive Microglia in AD through H4 Histone Lactation
投稿时间:2023-08-16  修订日期:2023-09-11
DOI:10.13241/j.cnki.pmb.2024.03.001
中文关键词: 阿尔茨海默病  瞬时受体电位香草素1型  小胶质细胞  H4K12la
英文关键词: Alzheimer's disease  TRPV1  Microglia  H4K12la
基金项目:国家自然科学基金项目(82173791);上海市自然科学基金项目(23ZR1436600)
作者单位E-mail
沙旭栋 上海交通大学医学院药理学与化学生物学系 上海 200025 ahmushaxudong@163.com 
鲁 佳 上海交通大学医学院药理学与化学生物学系 上海 200025  
林佳源 上海交通大学医学院药理学与化学生物学系 上海 200025  
黄立栋 上海交通大学医学院药理学与化学生物学系 上海 200025  
马小莉 上海交通大学医学院药理学与化学生物学系 上海 200025  
虞志华 上海交通大学医学院药理学与化学生物学系 上海 200025  
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中文摘要:
      摘要 目的:阿尔茨海默病(AD)中小胶质细胞的免疫监测和吞噬功能逐渐减弱并发生炎症激活。以往研究报道瞬时受体电位香草素1型(TRPV1)通道的激活可以缓解3xTg小鼠脑内小胶质细胞的炎症激活和吞噬功能障碍,作用机制尚不清楚。方法:首先,通过蛋白印迹法和免疫荧光实验测量3xTg小鼠大脑细胞核内组蛋白H4的12位赖氨酸乳酸化(H4K12la)的表达水平和细胞定位情况。其次,验证TRPV1的激活是否可以调控3xTg小鼠大脑细胞核内H4K12la的表达水平。最后,使用Imaris软件和流式细胞术分析TRPV1的激活对小胶质细胞炎症激活形态和生物标志物的影响。结果:蛋白印迹法显示3xTg小鼠大脑细胞核内H4K12la的表达水平上升,免疫荧光实验证明H4K12la与小胶质细胞共定位。TRPV1的激活可以减少3xTg小鼠脑内小胶质细胞中H4K12la的表达水平,缓解3xTg小鼠脑内小胶质细胞炎症激活。结论:TRPV1可以通过抑制组蛋白H4K12la表达缓解AD小胶质细胞炎症激活。
英文摘要:
      ABSTRACT Objective: The immune monitoring and phagocytosis function of microglia in Alzheimer's disease (AD) is progressively weakened and inflammatory activation occurs. Previous studies have reported that activation of transient receptor potential vanilloid type 1 (TRPV1) channels alleviates microglial inflammatory activation and phagocytosis dysfunction in the brain of 3xTg mice, and the mechanism of action is still unclear. Methods: First, the expression level and cellular localization of H4K12la in the nuclei of 3xTg mice brain cells were measured by western blotting and immunofluorescence experiments. Second, it was verified whether activation of TRPV1 could regulate the expression level of H4K12la in the nuclei of 3xTg mice brain cells. Finally, the effects of TRPV1 activation on microglia inflammatory activation morphology and biomarkers were analyzed using Imaris software and flow cytometry. Results: Western blotting showed increased expression levels of H4K12la in the nuclei of 3xTg mice brain cells, and immunofluorescence experiments demonstrated that H4K12la co-localized with microglia. Activation of TRPV1 reduced the expression levels of H4K12la in microglia and alleviated inflammatory activation of microglia in the brain of 3xTg mice. Conclusion: These findings suggest that TRPV1 can alleviate AD microglia inflammatory activation by inhibiting histone H4K12la expression.
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