• 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

阿佩林和埃拉贝拉唑配体对阿佩林受体不同信号通路的影响。

The Effects of Apelin and Elabela Ligands on Apelin Receptor Distinct Signaling Profiles.

作者信息

Jiang Yunlu, Yan Maocai, Wang Chunmei, Wang Qinqin, Chen Xiaoyu, Zhang Rumin, Wan Lei, Ji Bingyuan, Dong Bo, Wang Huiyun, Chen Jing

机构信息

Neurobiology Key Laboratory of Jining Medical University in Colleges of Shandong, Jining Medical University, Jining, China.

School of Pharmacy, Jining Medical University, Shandong, China.

出版信息

Front Pharmacol. 2021 Mar 4;12:630548. doi: 10.3389/fphar.2021.630548. eCollection 2021.

DOI:10.3389/fphar.2021.630548
PMID:33746758
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7970304/
Abstract

Apelin and Elabela are endogenous peptide ligands for Apelin receptor (APJ), a widely expressed G protein-coupled receptor. They constitute a spatiotemporal dual ligand system to control APJ signal transduction and function. We investigated the effects of Apelin-13, pGlu-apelin-13, Apelin-17, Apelin-36, Elabela-21 and Elabela-32 peptides on APJ signal transduction. Whether different ligands are biased to different APJ mediated signal transduction pathways was studied. We observed the different changes of G protein dependent and β-arrestin dependent signaling pathways after APJ was activated by six peptide ligands. We demonstrated that stimulation with APJ ligands resulted in dose-dependent increases in both G protein dependent [cyclic AMP (cAMP), Ca mobilization, and the early phase extracellular related kinase (ERK) activation] and β-arrestin dependent [GRKs, β-arrestin 1, β-arrestin 2, and β2 subunit of the clathrin adaptor AP2] signaling pathways. However, the ligands exhibited distinct signaling profiles. Elabela-32 showed a >1000-fold bias to the β-statin-dependent signaling pathway. These data provide that Apelin-17 was biased toward β-arrestin dependent signaling. Eabela-21 and pGlu-Apelin-13 exhibited very distinct activities on the G protein dependent pathway. The activity profiles of these ligands could be valuable for the development of drugs with high selectivity for specific APJ downstream signaling pathways.

摘要

Apelin和Elabela是Apelin受体（APJ）的内源性肽配体，APJ是一种广泛表达的G蛋白偶联受体。它们构成一个时空双配体系统，以控制APJ信号转导和功能。我们研究了Apelin-13、pGlu-apelin-13、Apelin-17、Apelin-36、Elabela-21和Elabela-32肽对APJ信号转导的影响。研究了不同配体是否偏向于不同的APJ介导的信号转导途径。我们观察了六种肽配体激活APJ后G蛋白依赖性和β-抑制蛋白依赖性信号通路的不同变化。我们证明，用APJ配体刺激会导致G蛋白依赖性[环磷酸腺苷（cAMP）、钙动员和早期细胞外相关激酶（ERK）激活]和β-抑制蛋白依赖性[G蛋白偶联受体激酶（GRKs）、β-抑制蛋白1、β-抑制蛋白2和网格蛋白衔接蛋白AP2的β2亚基]信号通路呈剂量依赖性增加。然而，这些配体表现出不同的信号特征。Elabela-32对β-抑制蛋白依赖性信号通路的偏向性>1000倍。这些数据表明Apelin-17偏向于β-抑制蛋白依赖性信号。Eabela-21和pGlu-Apelin-13在G蛋白依赖性途径上表现出非常不同的活性。这些配体的活性特征对于开发对特定APJ下游信号通路具有高选择性的药物可能具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/60634b1263ea/fphar-12-630548-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/eba89b21bde3/fphar-12-630548-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/83454732e577/fphar-12-630548-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/b8fab7ea811a/fphar-12-630548-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/f0e11b3e8a71/fphar-12-630548-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/10ca9a54a00b/fphar-12-630548-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/6c2eb2bf4da5/fphar-12-630548-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/037235c04519/fphar-12-630548-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/cb4cefe13b04/fphar-12-630548-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/6e805d036e8e/fphar-12-630548-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/60634b1263ea/fphar-12-630548-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/eba89b21bde3/fphar-12-630548-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/83454732e577/fphar-12-630548-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/b8fab7ea811a/fphar-12-630548-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/f0e11b3e8a71/fphar-12-630548-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/10ca9a54a00b/fphar-12-630548-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/6c2eb2bf4da5/fphar-12-630548-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/037235c04519/fphar-12-630548-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/cb4cefe13b04/fphar-12-630548-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/6e805d036e8e/fphar-12-630548-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5986/7970304/60634b1263ea/fphar-12-630548-g010.jpg

相似文献

1
The Effects of Apelin and Elabela Ligands on Apelin Receptor Distinct Signaling Profiles.阿佩林和埃拉贝拉唑配体对阿佩林受体不同信号通路的影响。
Front Pharmacol. 2021 Mar 4;12:630548. doi: 10.3389/fphar.2021.630548. eCollection 2021.
2
Individual phosphorylation sites at the C-terminus of the apelin receptor play different roles in signal transduction.阿利吉仑在体内的半衰期约为 6 小时，其主要通过粪便排泄，约 70%以原型形式排出。
Redox Biol. 2020 Sep;36:101629. doi: 10.1016/j.redox.2020.101629. Epub 2020 Jun 30.
3
Apelin and Elabela/Toddler; double ligands for APJ/Apelin receptor in heart development, physiology, and pathology.Apelin 和 Elabela/Toddler；APJ/Apelin 受体在心脏发育、生理和病理中的双重配体。
Peptides. 2019 Jan;111:62-70. doi: 10.1016/j.peptides.2018.04.011. Epub 2018 Apr 21.
4
Elabela/Toddler and apelin bind differently to the apelin receptor.埃拉贝拉/幼儿和阿片肽以不同的方式与阿片肽受体结合。
FASEB J. 2020 Jun;34(6):7989-8000. doi: 10.1096/fj.201903029R. Epub 2020 Apr 17.
5
Gαi-biased apelin analog protects against isoproterenol-induced myocardial dysfunction in rats.G 蛋白偶联受体偏倚型阿利肽类似物可预防异丙肾上腺素诱导的大鼠心肌功能障碍。
Am J Physiol Heart Circ Physiol. 2021 Apr 1;320(4):H1646-H1656. doi: 10.1152/ajpheart.00688.2020. Epub 2021 Feb 26.
6
Identification of serine 348 on the apelin receptor as a novel regulatory phosphorylation site in apelin-13-induced G protein-independent biased signaling.鉴定出阿片肽受体丝氨酸 348 是阿皮素-13 诱导的 G 蛋白非依赖性偏倚信号传导中的一个新的调节性磷酸化位点。
J Biol Chem. 2014 Nov 7;289(45):31173-87. doi: 10.1074/jbc.M114.574020. Epub 2014 Sep 30.
7
GPCR structure and function relationship: identification of a biased apelin receptor mutant.G 蛋白偶联受体结构与功能关系：偏倚性阿片肽受体突变体的鉴定。
Biochem J. 2018 Dec 6;475(23):3813-3826. doi: 10.1042/BCJ20180740.
8
Elabela-apelin-12, 17, 36/APJ system promotes platelet aggregation and thrombosis via activating the PANX1-P2X7 signaling pathway.埃拉贝拉-阿普林-12、17、36/APJ 系统通过激活 PANX1-P2X7 信号通路促进血小板聚集和血栓形成。
J Cell Biochem. 2023 Apr;124(4):586-605. doi: 10.1002/jcb.30392. Epub 2023 Mar 1.
9
Apela Regulates Fluid Homeostasis by Binding to the APJ Receptor to Activate Gi Signaling.Apela通过与APJ受体结合以激活Gi信号传导来调节液体稳态。
J Biol Chem. 2015 Jul 24;290(30):18261-8. doi: 10.1074/jbc.M115.648238. Epub 2015 May 20.
10
Comparative Study of Elabela and Apelin on Apelin Receptor Activation Through β-Arrestin Recruitment.埃拉贝拉和 Apelin 通过β-arrestin 募集对 Apelin 受体激活的比较研究。
Mol Biotechnol. 2023 Mar;65(3):394-400. doi: 10.1007/s12033-022-00529-6. Epub 2022 Aug 12.

引用本文的文献

1
In vivo measurement of an Apelin gradient with a genetically encoded APLNR conformation biosensor.使用基因编码的APLNR构象生物传感器对阿片肽梯度进行体内测量。
Nat Commun. 2025 Jul 21;16(1):6682. doi: 10.1038/s41467-025-61781-3.
2
The significance of the apelinergic system in doxorubicin-induced cardiotoxicity.阿片肽能系统在阿霉素诱导的心脏毒性中的意义。
Heart Fail Rev. 2024 Sep;29(5):969-988. doi: 10.1007/s10741-024-10414-w. Epub 2024 Jul 11.
3
Advances in the study of ELABELA in renal physiological functions and related diseases.

本文引用的文献

1
Oliceridine: First Approval.奥列西定：首次批准。
Drugs. 2020 Nov;80(16):1739-1744. doi: 10.1007/s40265-020-01414-9.
2
Individual phosphorylation sites at the C-terminus of the apelin receptor play different roles in signal transduction.阿利吉仑在体内的半衰期约为 6 小时，其主要通过粪便排泄，约 70%以原型形式排出。
Redox Biol. 2020 Sep;36:101629. doi: 10.1016/j.redox.2020.101629. Epub 2020 Jun 30.
3
Elabela/Toddler and apelin bind differently to the apelin receptor.埃拉贝拉/幼儿和阿片肽以不同的方式与阿片肽受体结合。
埃拉贝拉（ELABELA）在肾脏生理功能及相关疾病研究中的进展
Front Pharmacol. 2023 Oct 31;14:1276488. doi: 10.3389/fphar.2023.1276488. eCollection 2023.
4
Apelin prevents diabetes-induced poor collateral vessel formation and blood flow reperfusion in ischemic limb.阿帕琳可预防糖尿病引起的缺血肢体侧支血管形成不良和血流再灌注。
Front Cardiovasc Med. 2023 Aug 11;10:1191891. doi: 10.3389/fcvm.2023.1191891. eCollection 2023.
5
Signaling Modulation via Minimal C-Terminal Modifications of Apelin-13.通过对Apelin-13的最小C末端修饰进行信号调节。
ACS Pharmacol Transl Sci. 2023 Jan 26;6(2):290-305. doi: 10.1021/acsptsci.2c00219. eCollection 2023 Feb 10.
6
ERK/HIF-1α/VEGF pathway: a molecular target of ELABELA (ELA) peptide for attenuating cardiac ischemia-reperfusion injury in rats by promoting angiogenesis.ERK/HIF-1α/VEGF 通路：ELABELA（ELA）肽通过促进血管生成减轻大鼠心肌缺血再灌注损伤的分子靶点。
Mol Biol Rep. 2022 Nov;49(11):10509-10519. doi: 10.1007/s11033-022-07818-y. Epub 2022 Sep 21.
7
Possible roles of exercise and apelin against pregnancy complications.运动和 Apelin 在对抗妊娠并发症中的可能作用。
Front Endocrinol (Lausanne). 2022 Aug 25;13:965167. doi: 10.3389/fendo.2022.965167. eCollection 2022.
8
Apelin Resistance Contributes to Muscle Loss during Cancer Cachexia in Mice.阿片肽抵抗导致小鼠癌症恶病质期间的肌肉损失。
Cancers (Basel). 2022 Apr 2;14(7):1814. doi: 10.3390/cancers14071814.
9
Amidation-Modified Apelin-13 Regulates PPAR and Perilipin to Inhibit Adipogenic Differentiation and Promote Lipolysis.酰胺化修饰的Apelin-13调节过氧化物酶体增殖物激活受体（PPAR）和脂滴包被蛋白以抑制脂肪生成分化并促进脂肪分解。
Bioinorg Chem Appl. 2021 May 7;2021:3594630. doi: 10.1155/2021/3594630. eCollection 2021.
FASEB J. 2020 Jun;34(6):7989-8000. doi: 10.1096/fj.201903029R. Epub 2020 Apr 17.
4
International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand.国际基础和临床药理学联合会。CVII. 阿皮林受体的结构和药理学，建议埃拉贝拉/幼童是第二种内源性肽配体。
Pharmacol Rev. 2019 Oct;71(4):467-502. doi: 10.1124/pr.119.017533.
5
Apelin-36-[L28A] and Apelin-36-[L28C(30kDa-PEG)] peptides that improve diet induced obesity are G protein biased ligands at the apelin receptor.Apelin-36-[L28A] 和 Apelin-36-[L28C(30kDa-PEG)] 肽可改善饮食诱导的肥胖，它们是一种 G 蛋白偏向配体，作用于 Apelin 受体。
Peptides. 2019 Nov;121:170139. doi: 10.1016/j.peptides.2019.170139. Epub 2019 Aug 28.
6
The apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders.阿皮林能系统：心血管和代谢紊乱挑战与机遇的新视角。
Ann N Y Acad Sci. 2019 Nov;1455(1):12-33. doi: 10.1111/nyas.14123. Epub 2019 Jun 25.
7
Ghrelin Through GHSR1a and OX1R Heterodimers Reveals a Gαs-cAMP-cAMP Response Element Binding Protein Signaling Pathway .通过生长激素促分泌素受体1a（GHSR1a）和食欲素受体1（OX1R）异二聚体的胃饥饿素揭示了一条Gαs-环磷酸腺苷-环磷酸腺苷反应元件结合蛋白信号通路。
Front Mol Neurosci. 2018 Jul 17;11:245. doi: 10.3389/fnmol.2018.00245. eCollection 2018.
8
Apelin and Elabela/Toddler; double ligands for APJ/Apelin receptor in heart development, physiology, and pathology.Apelin 和 Elabela/Toddler；APJ/Apelin 受体在心脏发育、生理和病理中的双重配体。
Peptides. 2019 Jan;111:62-70. doi: 10.1016/j.peptides.2018.04.011. Epub 2018 Apr 21.
9
Biased signalling: from simple switches to allosteric microprocessors.偏向信号传导：从简单的开关到别构微处理器。
Nat Rev Drug Discov. 2018 Apr;17(4):243-260. doi: 10.1038/nrd.2017.229. Epub 2018 Jan 5.
10
ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice.ELABELA 缺乏可促进小鼠子痫前期和心血管畸形。
Science. 2017 Aug 18;357(6352):707-713. doi: 10.1126/science.aam6607. Epub 2017 Jun 29.