• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

鸟苷酸结合蛋白 2b 通过调控 AMPK/mTOR/ULK1 信号通路诱导 感染时的自噬。

Guanylate-Binding protein 2b regulates the AMPK/mTOR/ULK1 signalling pathway to induce autophagy during infection.

机构信息

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

出版信息

Virulence. 2022 Dec;13(1):875-889. doi: 10.1080/21505594.2022.2073024.

DOI:10.1080/21505594.2022.2073024
PMID:35531887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9132469/
Abstract

Autophagic isolation and degradation of intracellular pathogens are employed by host cells as primary innate immune defense mechanisms to control intercellular infection. In this study, RNA-Seq technology was used to obtain the total mRNA from bone marrow-derived macrophages (BMDMs) infected with at 6 and 24 h after infection. One of the differential genes, GBP2b, was also investigated. Analysis of the significant pathway involved in GBP2b-coexpressed mRNA demonstrated that GBP2b was associated with autophagy and autophagy-related mammalian target of rapamycin (mTOR) signaling and AMP-activated protein kinase (AMPK) signaling. The results of in vivo and in vitro experiments showed significant up-regulation of GBP2b during infection. For in vitro validation, small interfering RNA-GBP2b plasmids were transfected into BMDMs and RAW264.7 cells lines to down-regulate the expression of GBP2b. The results showed that the down-regulation of GBP2b impaired autophagy via the AMPK/mTOR/ULK1 pathway, thereby promoting the intracellular survival of . Further studies revealed that the activation of AMPK signaling was essential for the regulation of autophagy during infection. These findings expand the understanding of how GBP2b regulates autophagy and suggest that GBP2b may be a potential target for the treatment of diseases caused by .

摘要

自噬隔离和降解细胞内病原体被宿主细胞用作主要的先天免疫防御机制，以控制细胞间感染。在本研究中，采用 RNA-Seq 技术从感染 后 6 和 24 小时的骨髓来源巨噬细胞 (BMDM) 中获得总 mRNA。还研究了其中一个差异基因 GBP2b。对与 GBP2b 共表达 mRNA 相关的显著途径的分析表明，GBP2b 与自噬和自噬相关的哺乳动物雷帕霉素靶蛋白 (mTOR) 信号和 AMP 激活蛋白激酶 (AMPK) 信号有关。体内和体外实验的结果表明，在 感染过程中 GBP2b 显著上调。为了进行体外验证，将 GBP2b 小干扰 RNA 质粒转染到 BMDM 和 RAW264.7 细胞系中以下调 GBP2b 的表达。结果表明，GBP2b 的下调通过 AMPK/mTOR/ULK1 途径损害自噬，从而促进 的细胞内存活。进一步的研究表明，AMPK 信号的激活对于 感染过程中自噬的调节是必不可少的。这些发现扩展了对 GBP2b 如何调节自噬的理解，并表明 GBP2b 可能是治疗由 引起的疾病的潜在靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/d1fe4ddb1c2b/KVIR_A_2073024_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/1182d6807973/KVIR_A_2073024_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/aa2851b6aaba/KVIR_A_2073024_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/c614c3b2d315/KVIR_A_2073024_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/530b3cbd2ba5/KVIR_A_2073024_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/104fb7b03af9/KVIR_A_2073024_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/9e777419276a/KVIR_A_2073024_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/8b540d3a3fe7/KVIR_A_2073024_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/d1fe4ddb1c2b/KVIR_A_2073024_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/1182d6807973/KVIR_A_2073024_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/aa2851b6aaba/KVIR_A_2073024_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/c614c3b2d315/KVIR_A_2073024_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/530b3cbd2ba5/KVIR_A_2073024_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/104fb7b03af9/KVIR_A_2073024_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/9e777419276a/KVIR_A_2073024_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/8b540d3a3fe7/KVIR_A_2073024_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a9/9132469/d1fe4ddb1c2b/KVIR_A_2073024_F0008_B.jpg

相似文献

1
Guanylate-Binding protein 2b regulates the AMPK/mTOR/ULK1 signalling pathway to induce autophagy during infection.鸟苷酸结合蛋白 2b 通过调控 AMPK/mTOR/ULK1 信号通路诱导 感染时的自噬。
Virulence. 2022 Dec;13(1):875-889. doi: 10.1080/21505594.2022.2073024.
2
Digitoxin Suppresses Human Cytomegalovirus Replication via Na, K/ATPase α1 Subunit-Dependent AMP-Activated Protein Kinase and Autophagy Activation.洋地黄毒苷通过钠钾ATP酶α1亚基依赖的AMP激活蛋白激酶和自噬激活抑制人巨细胞病毒复制。
J Virol. 2018 Feb 26;92(6). doi: 10.1128/JVI.01861-17. Print 2018 Mar 15.
3
[Effect of electroacupuncture on hepatocyte autophagy and oxidative stress in SAMP8 mice by regulating AMPK/mTOR/ULK1 signaling pathway].[电针通过调节AMPK/mTOR/ULK1信号通路对SAMP8小鼠肝细胞自噬和氧化应激的影响]
Zhen Ci Yan Jiu. 2022 Jan 25;47(1):7-14. doi: 10.13702/j.1000-0607.201244.
4
Toll-like receptor signalling cross-activates the autophagic pathway to restrict Salmonella Typhimurium growth in macrophages.Toll 样受体信号交叉激活自噬途径以限制巨噬细胞中鼠伤寒沙门氏菌的生长。
Cell Microbiol. 2019 Dec;21(12):e13095. doi: 10.1111/cmi.13095. Epub 2019 Aug 26.
5
PP2Ac Modulates AMPK-Mediated Induction of Autophagy in -Infected Macrophages.PP2Ac 调节 AMPK 介导的感染巨噬细胞中的自噬诱导。
Int J Mol Sci. 2019 Nov 29;20(23):6030. doi: 10.3390/ijms20236030.
6
The serine/threonine kinase ULK1 is a target of multiple phosphorylation events.丝氨酸/苏氨酸激酶 ULK1 是多个磷酸化事件的靶标。
Biochem J. 2011 Dec 1;440(2):283-91. doi: 10.1042/BJ20101894.
7
The association of AMPK with ULK1 regulates autophagy.AMPK 与 ULK1 的关联调节自噬。
PLoS One. 2010 Nov 3;5(11):e15394. doi: 10.1371/journal.pone.0015394.
8
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.AMPK 和 mTOR 通过直接磷酸化 Ulk1 来调节自噬。
Nat Cell Biol. 2011 Feb;13(2):132-41. doi: 10.1038/ncb2152. Epub 2011 Jan 23.
9
Nilotinib: A Tyrosine Kinase Inhibitor Mediates Resistance to Intracellular Mycobacterium Via Regulating Autophagy.尼洛替尼：一种通过调节自噬介导细胞内分枝杆菌耐药的酪氨酸激酶抑制剂。
Cells. 2019 May 26;8(5):506. doi: 10.3390/cells8050506.
10
AMPK and mTOR coordinate the regulation of Ulk1 and mammalian autophagy initiation.AMPK 和 mTOR 协调 Ulk1 的调节和哺乳动物自噬的起始。
Autophagy. 2011 Aug;7(8):924-6. doi: 10.4161/auto.7.8.15860. Epub 2011 Aug 1.

引用本文的文献

1
Guanylate-binding protein-5 is involved in inflammasome activation by bacterial DNA but only the cooperation of multiple GBPs accounts for control of infection.鸟苷酸结合蛋白-5 参与细菌 DNA 引发的炎症小体激活，但只有多种 GBP 的合作才能控制感染。
Front Immunol. 2024 Feb 8;15:1341464. doi: 10.3389/fimmu.2024.1341464. eCollection 2024.

本文引用的文献

1
RipA Dampens TLR4-Mediated Host Protective Response Using a Multi-Pronged Approach Involving Autophagy, Apoptosis, Metabolic Repurposing, and Immune Modulation.RipA 通过多种途径（包括自噬、细胞凋亡、代谢重编程和免疫调节）削弱 TLR4 介导的宿主保护反应。
Front Immunol. 2021 Mar 4;12:636644. doi: 10.3389/fimmu.2021.636644. eCollection 2021.
2
Contributes to M1 Macrophage Polarization in ARDS.有助于 ARDS 中的 M1 巨噬细胞极化。
Front Immunol. 2021 Jan 14;11:580838. doi: 10.3389/fimmu.2020.580838. eCollection 2020.
3
Bisphenol A promotes autophagy in ovarian granulosa cells by inducing AMPK/mTOR/ULK1 signalling pathway.
双酚 A 通过诱导 AMPK/mTOR/ULK1 信号通路促进卵巢颗粒细胞自噬。
Environ Int. 2021 Feb;147:106298. doi: 10.1016/j.envint.2020.106298. Epub 2020 Dec 30.
4
MicroRNA-20a-3p regulates the host immune response to facilitate the mycobacterium tuberculosis infection by targeting IKKβ/NF-κB pathway.微小 RNA-20a-3p 通过靶向 IKKβ/NF-κB 通路调控宿主免疫反应促进结核分枝杆菌感染。
Int Immunopharmacol. 2021 Feb;91:107286. doi: 10.1016/j.intimp.2020.107286. Epub 2020 Dec 29.
5
Crosstalk Between Astrocytes and Microglia: An Overview.星形胶质细胞和小胶质细胞之间的串扰：概述。
Front Immunol. 2020 Jul 16;11:1416. doi: 10.3389/fimmu.2020.01416. eCollection 2020.
6
Captain GBP1: inflammasomes assemble, pyroptotic endgame.英国英镑队长1：炎性小体组装，细胞焦亡终局。
Nat Immunol. 2020 Aug;21(8):829-830. doi: 10.1038/s41590-020-0727-0.
7
Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria.人 GBP1 结合 LPS 以启动细胞质细菌中 caspase-4 激活平台的组装。
Nat Commun. 2020 Jun 24;11(1):3276. doi: 10.1038/s41467-020-16889-z.
8
Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms.鸟苷酸结合蛋白将细胞质内的细菌转化为半胱天冬酶-4 信号平台。
Nat Immunol. 2020 Aug;21(8):880-891. doi: 10.1038/s41590-020-0697-2. Epub 2020 Jun 15.
9
BAG2 ameliorates endoplasmic reticulum stress-induced cell apoptosis in -infected macrophages through selective autophagy.BAG2 通过选择性自噬改善 - 感染巨噬细胞中的内质网应激诱导的细胞凋亡。
Autophagy. 2020 Aug;16(8):1453-1467. doi: 10.1080/15548627.2019.1687214. Epub 2019 Nov 11.
10
Brain-penetrant PQR620 mTOR and PQR530 PI3K/mTOR inhibitor reduce huntingtin levels in cell models of HD.穿透血脑屏障的 PQR620 mTOR 和 PQR530 PI3K/mTOR 抑制剂可降低 HD 细胞模型中的亨廷顿蛋白水平。
Neuropharmacology. 2020 Jan 1;162:107812. doi: 10.1016/j.neuropharm.2019.107812. Epub 2019 Oct 14.