Background: The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA.
Objective: To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation.
Methods: Male Wistar rats were randomly distributed into two groups: control (n = 14), fed with normocaloric diet; and obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP-1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed by Western blot.
Results: Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16.
Conclusion: Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system.
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http://dx.doi.org/10.5935/abc.20140083 | DOI Listing |
Cells
December 2024
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institute of Health, Baltimore, MD 21224, USA.
The spontaneous firing of the sinoatrial (SA) node, the physiological pacemaker of the heart, is generated within sinoatrial nodal cells (SANCs) and is regulated by a "coupled-clock" pacemaker system, which integrates a "membrane clock", the ensemble of ion channel currents, and an intracellular "Ca clock", sarcoplasmic reticulum-generated local submembrane Ca releases via ryanodine receptors. The interactions within a "coupled-clock" system are modulated by phosphorylation of surface membrane and sarcoplasmic reticulum proteins. Though the essential role of a high basal cAMP level and PKA-dependent phosphorylation for basal spontaneous SANC firing is well recognized, the role of basal CaMKII-dependent phosphorylation remains uncertain.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
The ability to efficiently make precise genome edits in somatic tissues will have profound implications for gene therapy and basic science. CRISPR/Cas9 mediated homology-directed repair (HDR) is one approach that is commonly used to achieve precise and efficient editing in cultured cells. Previously, we developed a platform capable of delivering CRISPR/Cas9 gRNAs and donor templates via adeno-associated virus to induce HDR (CASAAV-HDR).
View Article and Find Full Text PDFBr J Pharmacol
December 2024
Department of Pharmacology, University of California, Davis, Davis, California, USA.
Background And Purpose: Sarcoplasmic reticulum Ca-ATPase (SERCA2a) is impaired in heart failure. Phosphodiesterases (PDEs) are implicated in the modulation of local cAMP signals and protein kinase A (PKA) activity essential for cardiac function. We characterise PDE isoforms that underlie decreased activities of SERCA2a and reduced cardiac contractile function in diabetic cardiomyopathy.
View Article and Find Full Text PDFAcupunct Med
December 2024
Institute of Acupuncture and Meridian, Anhui University of Chinese Medicine, Hefei, China.
Objective: To determine the effect of electroacupuncture (EA) on β-adrenergic receptor (β-AR) and post-receptor protein kinase A (PKA) signaling pathway after acute myocardial ischemia (MI).
Methods: An MI model was established by ligating the left anterior descending coronary artery of wild-type (WT) C57/BL and β-AR mice (heterozygous for β-AR gene deletion). EA treatment was administered at HT5-HT7 or LU9-LU8.
Biophys Rep
October 2024
Cyrus Tang Medical Institute, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu 215123, China.
β-adrenergic receptors (βARs) play significant roles in regulating Ca signaling in cardiac myocytes, thus holding a key function in modulating heart performance. βARs regulate the influx of extracellular Ca and the release and uptake of Ca from the sarcoplasmic reticulum (SR) by activating key components such as L-type calcium channels (LTCCs), ryanodine receptors (RyRs) and phospholamban (PLN), mediated by the phosphorylation actions by protein kinase A (PKA). In cardiac myocytes, the presence of βAR provides a protective mechanism against potential overstimulation of βAR, which may aid in the restoration of cardiac dysfunctions.
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