ArticleBiochimica et biophysica acta. General subjects2017
Bioactivity of the putative apelin proprotein expands the repertoire of apelin receptor ligands.
Article in Biochimica et biophysica acta. General subjects, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- Targeting the Apelin-APJ Axis: A Promising Strategy to Mitigate Anthracycline-Induced Cardiotoxicity.Cardiovascular toxicology · 2026Review
- Gastric and Small-Intestinal Morphological Remodeling After Intragastric Apelin-13 Administration in Unweaned Rats.Animals : an open access journal from MDPI · 2026Article
- A reactive oxygen species-responsive hydrogel loaded with Apelin-13 promotes the repair of spinal cord injury by regulating macrophage M1/M2 polarization and neuroinflammation.Journal of nanobiotechnology · 2025Article
- Diagnostic and prognostic significance of apelin-13, APJ for sepsis in the emergency department: A prospective study.Heliyon · 2024Article
- Exploring the potential roles of apelin, visfatin, and irisin in energy regulation in farm animals: an overview.Frontiers in veterinary science · 2024Review
- QN-302 demonstrates opposing effects between i-motif and G-quadruplex DNA structures in the promoter of the S100P gene.Organic & biomolecular chemistry · 2023Article
- Exploring the Network between Adipocytokines and Inflammatory Response in SARS-CoV-2 Infection: A Scoping Review.Nutrients · 2023Article
- Structure-function relationship and physiological role of apelin and its G protein coupled receptor.Biophysical reviews · 2023Review
- Advances in the study of ELABELA in renal physiological functions and related diseases.Frontiers in pharmacology · 2023Review
- A Review of the Roles of Apelin and ELABELA Peptide Ligands in Cardiovascular Disease, Including Heart Failure and Hypertension.Medical science monitor : international medical journal of experimental and clinical research · 2022Review
- Review
- Circulating Levels of Apelin, GDF-15 and Sarcopenia: Lack of Association in the MAPT Study.The journal of nutrition, health & aging · 2022Article
- Potential Therapeutic Role for Apelin and Related Peptides in Diabetes: An Update.Clinical medicine insights. Endocrinology and diabetes · 2022Review
- Amidation-Modified Apelin-13 Regulates PPARBioinorganic chemistry and applications · 2021Article
- The Effects of Apelin and Elabela Ligands on Apelin Receptor Distinct Signaling Profiles.Frontiers in pharmacology · 2021Article
- Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells.Molecular and cellular biochemistry · 2019Article
- Simultaneous Ligand and Receptor Tracking through NMR Spectroscopy Enabled by DistinctInternational journal of molecular sciences · 2019Article
- Proapelin is processed extracellularly in a cell line-dependent manner with clear modulation by proprotein convertases.Amino acids · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundApelin is a peptide ligand for a class A G-protein coupled receptor called the apelin receptor (AR or APJ) that regulates angiogenesis, the adipoinsular axis, and cardiovascular functions. Apelin has been shown to be bioactive as 13, 17, and 36 amino acid isoforms, C-terminal fragments of the putatively inactive 55-residue proprotein (proapelin or apelin-55). Although intracellular proprotein processing has been proposed, isolation of apelin-55 from colostrum and milk demonstrates potential for secretion prior to processing and the possibility of proapelin-AR interaction.
methodsApelin isoform activity and potency were compared by an In-Cell Western™ assay for ERK phosphorylation using a stably AR-transfected HEK293A cell line. Conformational comparison of apelin isoforms was carried out by circular dichroism and heteronuclear solution-state nuclear magnetic resonance spectroscopy.
resultsApelin-55 is shown to activate the AR, with similar maximum ERK phophorylation response and potency to the shorter isoforms except for apelin-13, which exhibited a greater potency. Correlating to this shared activity, highly similar conformations are exhibited in all apelin isoforms for the shared C-terminal region responsible for receptor binding and activation.
conclusionsAR activation by all apelin isoforms likely hinges upon shared conformation and dynamics in the C-terminus, with apelin-55 providing an alternative bioactive isoform despite the addition of 19N-terminal residues relative to apelin-36. GENERAL SIGNIFICANCE: Beyond providing novel insight into the physiology of this system, re-annotation of proapelin to the bioactive apelin-55 isoform adds to the molecular toolkit for dissection of apelin-AR interactions and expands the repertoire of therapeutic targets for the apelinergic system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.