Nitric Oxide and S-Nitrosylation in Cardiac Regulation: G Protein-Coupled Receptor Kinase-2 and β-Arrestins as Targets
| Autor: | Walter J. Koch, Gizem Kayki-Mutlu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
G-Protein-Coupled Receptor Kinase 2 GRK2 Review 030204 cardiovascular system & hematology Catalysis Nitric oxide Inorganic Chemistry lcsh:Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation nitric oxide Receptors Adrenergic beta Cyclic GMP-Dependent Protein Kinases Humans Physical and Theoretical Chemistry Molecular Biology Cyclic GMP lcsh:QH301-705.5 Spectroscopy beta-Arrestins G protein-coupled receptor β-arrestins G protein-coupled receptor kinase S-Nitrosothiols biology Kinase Chemistry Beta adrenergic receptor kinase Organic Chemistry General Medicine S-Nitrosylation S-nitrosylation Computer Science Applications Cell biology 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 biology.protein Nitric Oxide Synthase cGMP-dependent protein kinase Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 521, p 521 (2021) International Journal of Molecular Sciences |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Cardiac diseases including heart failure (HF), are the leading cause of morbidity and mortality globally. Among the prominent characteristics of HF is the loss of β-adrenoceptor (AR)-mediated inotropic reserve. This is primarily due to the derangements in myocardial regulatory signaling proteins, G protein-coupled receptor (GPCR) kinases (GRKs) and β-arrestins (β-Arr) that modulate β-AR signal termination via receptor desensitization and downregulation. GRK2 and β-Arr2 activities are elevated in the heart after injury/stress and participate in HF through receptor inactivation. These GPCR regulators are modulated profoundly by nitric oxide (NO) produced by NO synthase (NOS) enzymes through S-nitrosylation due to receptor-coupled NO generation. S-nitrosylation, which is NO-mediated modification of protein cysteine residues to generate an S-nitrosothiol (SNO), mediates many effects of NO independently from its canonical guanylyl cyclase/cGMP/protein kinase G signaling. Herein, we review the knowledge on the NO system in the heart and S-nitrosylation-dependent modifications of myocardial GPCR signaling components GRKs and β-Arrs. |
| Databáze: | OpenAIRE |
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