GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure

Laudette, Marion; Formoso, Karina; Lezoualc’h, Frank

doi:10.3390/cells10010154

Cited by 7 publications

(4 citation statements)

References 129 publications

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“…At present, GRKs are comprising seven isoforms (GRK1-7) in vertebrates. More importantly, GRK2 and 3 isoforms, the second subfamily named β-adrenergic receptor kinase subfamily, are ubiquitously expressed and generally localized to the cytosol and plasma membrane ( 14 ). Furthermore, recent studies have found that there are diverse changes in the expression and activity levels of GRK2 under pathophysiology conditions.…”

Section: Regulation Of Grk2 Activity Under Pathophysiology Conditionsmentioning

confidence: 99%

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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G protein-coupled receptor kinase 2 (GRK2), an important subtype of GRKs, specifically phosphorylates agonist-activated G protein-coupled receptors (GPCRs). Besides, current research confirms that it participates in multiple regulation of diverse cells via a non-phosphorylated pathway, including interacting with various non-receptor substrates and binding partners. Fibrosis is a common pathophysiological phenomenon in the repair process of many tissues due to various pathogenic factors such as inflammation, injury, drugs, etc. The characteristics of fibrosis are the activation of fibroblasts leading to myofibroblast proliferation and differentiation, subsequent aggerate excessive deposition of extracellular matrix (ECM). Then, a positive feedback loop is occurred between tissue stiffness caused by ECM and fibroblasts, ultimately resulting in distortion of organ architecture and function. At present, GRK2, which has been described as a multifunctional protein, regulates copious signaling pathways under pathophysiological conditions correlated with fibrotic diseases. Along with GRK2-mediated regulation, there are diverse effects on the growth and apoptosis of different cells, inflammatory response and deposition of ECM, which are essential in organ fibrosis progression. This review is to highlight the relationship between GRK2 and fibrotic diseases based on recent research. It is becoming more convincing that GRK2 could be considered as a potential therapeutic target in many fibrotic diseases.

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Section: Regulation Of Grk2 Activity Under Pathophysiology Conditionsmentioning

confidence: 99%

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

Shan

et al. 2022

Front. Immunol.

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“…This raises the question of the source of cAMP during viral infection. A possible explanation would be that virus entry could increase the pool of cAMP via the soluble adenyl cyclase (AC) which has been previously shown to regulate EPAC1 activation and endocytosis [ 22 , 23 , 24 ]. Consistently, it is suggested that soluble AC promotes endocytic pathway of viral entry by stimulating vacuolar ATPase-dependent acidification of endosomes and lysosomes [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

EPAC1 Pharmacological Inhibition with AM-001 Prevents SARS-CoV-2 and Influenza A Virus Replication in Cells

Foret‐Lucas

Figueroa

Bertin

et al. 2023

Viruses

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The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP). The cAMP-sensitive protein, EPAC1 regulates various physiological and pathological processes but its role in SARS-CoV-2 and influenza A virus infection has not yet been studied. Here, we provide evidence that the EPAC1 specific inhibitor AM-001 exerts potent antiviral activity against SARS-CoV-2 in the human lung Calu-3 cell line and the African green monkey Vero cell line. We observed a concentration-dependent inhibition of SARS-CoV-2 infectious viral particles and viral RNA release in the supernatants of AM-001 treated cells that was not associated with a significant impact on cellular viability. Furthermore, we identified AM-001 as an inhibitor of influenza A virus in Calu-3 cells. Altogether these results identify EPAC1 inhibition as a promising therapeutic target against viral infections.

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“…We cannot determine whether the activity of both toxins have a direct effect on the ß1 adrenergic and ß2 adrenergic receptors, both linked to increased chronotropism and inotropism of the cardiac muscle. These actions are due to the stimulating action on Protein G, which increases adenyl cyclase activity, causing high levels of cyclic AMP (34)(35)(36)(37). Gibbins (38) has suggested that the principal factor to take in consideration about the cardiotoxic effect has been the modulation of heart frequency that can be regularly measured by a direct optical examination, by video-edge detection systems.…”

Section: Discussionmentioning

confidence: 99%

Clinical cardiac alterations and hemostatic toxicities caused by scorpion (Tityus discrepans) venom and its purified fractions on zebrafish (Danio rerio) larvae

et al. 2021

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Envenomation by the Venezuelan scorpion Tityus discrepans is typified by local and systemic alterations. The current work investigated the in vivo hemostatic processes, cardiac dysfunction and tissue destruction triggered by Tityus discrepans purified toxins 1 (3 kDa) and 2 (5 kDa) fractions. These fractions were obtained by C-18-HPLC chromatography. The hemostatic and cardiovascular toxicities in zebrafish of both fractions was assessed by means of specific phenotypic expressions and larvae behavior at 5, 15, 30, 40 and 60 min post-venom-treatment. The Tityus discrepans venom fractions 1 and 2 produced disseminated intravascular coagulation (presence of thrombus) in the central vein of the larva, heart rate/rhythm alterations, and necrotic events in more than 90% of all the larvae under their action. The outcomes have established the potential hemostatic and cardiovascular toxicities by Tityus discrepans venom, alerting on the possibility of cardiovascular injuries and thromboembolism in humans after scorpion stings envenomation.

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GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure

Cited by 7 publications

References 129 publications

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases

EPAC1 Pharmacological Inhibition with AM-001 Prevents SARS-CoV-2 and Influenza A Virus Replication in Cells

Clinical cardiac alterations and hemostatic toxicities caused by scorpion (Tityus discrepans) venom and its purified fractions on zebrafish (Danio rerio) larvae

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