ArticleThe Journal of pharmacology and experimental therapeutics2016
Digoxin-Mediated Upregulation of RGS2 Protein Protects against Cardiac Injury.
Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Anticoagulation Therapies and microRNAs in Heart Failure.Biomolecules · 2025Review
- Discovery of RGS2-FBXO44 interaction inhibitors using a cell-based NanoBit assay.Molecular pharmacology · 2025Article
- ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Phenotypic High-Throughput Screen Identifies Small Molecule Modulators of Endogenous RGS10 in BV-2 Cells.Journal of medicinal chemistry · 2024Article
- RGS proteins and cardiovascular Angiotensin II Signaling: Novel opportunities for therapeutic targeting.Biochemical pharmacology · 2023Review
- Dual-omics reveals temporal differences in acute sympathetic stress-induced cardiac inflammation following αActa pharmacologica Sinica · 2023Article
- Article
- Dual loss of regulator of G protein signaling 2 and 5 exacerbates ventricular myocyte arrhythmias and disrupts the fine-tuning of GJournal of molecular and cellular cardiology · 2022Article
- Regulator of G protein signaling 2 inhibits GαThe Journal of biological chemistry · 2022Article
- A module of multifactor-mediated dysfunction guides the molecular typing of coronary heart disease.Molecular genetics & genomic medicine · 2020Article
- Periplocymarin Plays an Efficacious Cardiotonic RoleFrontiers in pharmacology · 2020Article
- Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials.The Journal of biological chemistry · 2019Review
- Na/K-ATPase Signaling and Cardiac Pre/Postconditioning with Cardiotonic Steroids.International journal of molecular sciences · 2018Review
- A current view of G protein-coupled receptor - mediated signaling in pulmonary hypertension: finding opportunities for therapeutic intervention.Vessel plus · 2018Article
- Proteolytic degradation of regulator of G protein signaling 2 facilitates temporal regulation of GThe Journal of biological chemistry · 2017Article
- The evolution of regulators of G protein signalling proteins as drug targets - 20 years in the making: IUPHAR Review 21.British journal of pharmacology · 2017Review
- Regulation of Cardiac Remodeling by Cardiac Na(+)/K(+)-ATPase Isoforms.Frontiers in physiology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Regulator of G protein signaling (RGS) proteins have emerged as novel drug targets since their discovery almost two decades ago. RGS2 has received particular interest in cardiovascular research due to its role in regulating Gqsignaling in the heart and vascular smooth muscle. RGS2(-/-)mice are hypertensive, prone to heart failure, and display accelerated kidney fibrosis. RGS2 is rapidly degraded through the proteasome, and human mutations leading to accelerated RGS2 protein degradation correlate with hypertension. Hence, stabilizing RGS2 protein expression could be a novel route in treating cardiovascular disease. We previously identified cardiotonic steroids, including digoxin, as selective stabilizers of RGS2 protein in vitro. In the current study we investigated the functional effects of digoxin-mediated RGS2 protein stabilization in vivo. Using freshly isolated myocytes from wild-type and RGS2(-/-)mice treated with vehicle or low-dose digoxin (2µg/kg/day for 7 days) we demonstrated that agonist-induced cAMP levels and cardiomyocyte contractility was inhibited by digoxin in wild-type but not in RGS2(-/-)mice. This inhibition was accompanied by an increase in RGS2 protein levels in cardiomyocytes as well as in whole heart tissue. Furthermore, digoxin had protective effects in a model of cardiac injury in wild-type mice and this protection was lost in RGS2(-/-)mice. Digoxin is the oldest known therapy for heart failure; however, beyond its activity at the Na(+)/K(+)-ATPase, the exact mechanism of action is not known. The current study adds a novel mechanism, whereby through stabilizing RGS2 protein levels digoxin could exert its protective effects in the failing heart.
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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.