Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Purpose: The aim of this study was to investigate whether eIF5A hypusine (eIF5A) reduces adenosine 2b receptor (A2bAR) gene expression through interaction with highly structured stem-loop sequences within the A2bAR 3'UTR.
Methods And Results: Based on real-time PCR and western blotting, expression of A2bAR mRNA was significantly decreased upon treatment with eIF5A in mouse embryonic fibroblasts of eIF5A (eIF5A-MEF) and 3T3-L1 cells. Target Scan software and RNAfold web server predicted two different structures formed by stem-loop sequences with overlapping microRNA 27 seed sequences and mutations. The EMSA results showed significantly impaired formation of the wild type (WT) biotin-labeled A2bAR probe (27 base) containing stem loop sequences-eIF5A complex by mutation of stem-loop sequences or by eIF5A non-hypusine (eIF5A). The luciferase reporter assay showed that GC7-induced eIF5A accumulation increased the activity of pMIR-A2bAR WT containing the same stem-loop sequence in 3T3-L1 cells, whereas the activity with pMIR-A2bAR Mut was increased compared to WT control without dependence on GC7. Oil Red O staining showed that suppression of A2bAR expression (A2bAR siRNA and eIF5A) increased the amount of lipid droplet formation and the mRNA levels of lipid droplet-related genes (C/EBP-β, PPAR-γ, FABP4, SREBP-1, and Perilipin). In contrast, overexpression of A2bAR (A2bAR vector, eIF5A vector, and GC7) significantly decreased the expression of lipid droplet-associated genes and lipid droplet formation.
Conclusions: eIF5A acts as a negative regulator of A2bAR gene expression through stem loop sequences in A2bAR 3'UTR, allowing differentiation of adipocytes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11033-023-08252-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular basis of ligand binding and receptor activation at the human A adenosine receptor.
Nat Commun
August 2025
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Adenosine receptors (ARs: AAR, AAR, AAR, and AAR) are crucial therapeutic targets; however, developing selective, efficacious drugs for them remains a significant challenge. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of the human AAR in three distinct functional states: bound to the endogenous agonist adenosine, the clinically relevant agonist Piclidenoson, and the covalent antagonist LUF7602. These structures, complemented by mutagenesis and pharmacological studies, reveal an AAR activation mechanism that involves an extensive hydrogen bond network from the extracellular surface down to the orthosteric binding site.
View Article and Find Full Text PDFAdenosine and adenosine receptors: a "double-edged sword" in cardiovascular system.
Front Pharmacol
July 2025
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Adenosine serves a variety of biological purposes in the circulatory system and was first discovered in the heart in 1929. By interacting with four adenosine receptor (AR) subtypes of G protein-coupled receptors-AAR, AAR, AAR, and AAR-adenosine controls physiological processes. In pathological situations, spikes in adenosine activate the four receptor subtypes and alter downstream pathways by altering the generation of cyclic adenosine monophosphate, which contributes to autophagy and inflammation.
View Article and Find Full Text PDFAdenosine A Receptor Antagonism Interferes with TGF-β Cellular Signaling Through SMAD2/-3 and p65-Nf-κB in Podocytes and Protects from Phenotypical Transformation in Experimental Diabetic Glomerulopathy.
Cells
June 2025
Molecular Pathology Laboratory, Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia 5110566, Chile.
Studies have emphasized alleviating fibrogenesis through interference with adenosine signaling in experimental diabetic nephropathy. We found that the in vivo antagonism of the adenosine A receptor (AAR) using MRS1754 in diabetic rats impedes the diabetes-induced glomerular expression of the mesenchymal-like transformation markers Snail and α-SMA, while the loss of the epithelial podocyte-specific proteins nephrin and ZO-1 was prevented. Furthermore, the production of MCP-1, CCL3, TGF-β, and the transcript levels of inflammatory mediators was reduced by AAR antagonism.
View Article and Find Full Text PDFA adenosine receptor-triggered intracellular calcium mobilization: Cell type-dependent involvement of G, G, G proteins and protein kinase C.
Purinergic Signal
June 2025
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bldg. 8A, Rm. B1A-23 9000 Rockville Pike, Bethesda, MD, 20892, USA.
Activation of PLCβ enzymes by G and G proteins is a common mechanism to trigger cytosolic Ca increase. We and others reported that G inhibitor FR900359 (FR) can inhibit both G- and, surprisingly, G-mediated intracellular Ca mobilization. Thus, the G-G-PLCβ-Ca signaling axis depends entirely on the presence of active G, which reasonably explained FR-inhibited G-induced Ca release.
View Article and Find Full Text PDFLigand and Residue Free Energy Perturbations Solve the Dual Binding Mode Proposal for an AAR Partial Agonist.
J Phys Chem B
January 2025
Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Box 596, Uppsala SE-75124, Sweden.
Adenosine receptors, particularly AAR, are gaining attention for their role in pathological conditions such as cancer immunotherapy, prompting the exploration for promising therapeutic applications. Despite numerous selective AAR antagonists, the lack of selective full agonists makes the partial agonist BAY60-6583 one of the most interesting activators of this receptor. Recent cryo-EM structures have univocally revealed the binding mode of nonselective ribosidic agonists such as adenosine and its derivative NECA to AAR; however, two independent structures with BAY60-6583 show alternative binding orientations, raising the question of which is the physiologically relevant binding mode.
View Article and Find Full Text PDF