scholarly journals β-Catenin Regulates Cardiac Energy Metabolism in Sedentary and Trained Mice

Life ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 357
Author(s):  
Volodymyr V. Balatskyi ◽  
Oksana L. Palchevska ◽  
Lina Bortnichuk ◽  
Ana-Maria Gan ◽  
Anna Myronova ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cardiac Hypertrophy ◽  
Endurance Training ◽  
Metabolic Regulation ◽  
Training Model ◽  
Cardiac Metabolism ◽  
Mitogen Activated Protein Kinase ◽  
Hypertrophic Growth ◽  
Physiological Cardiac Hypertrophy ◽  
Mitogen Activated Protein

The role of canonical Wnt signaling in metabolic regulation and development of physiological cardiac hypertrophy remains largely unknown. To explore the function of β-catenin in the regulation of cardiac metabolism and physiological cardiac hypertrophy development, we used mice heterozygous for cardiac-specific β-catenin knockout that were subjected to a swimming training model. β-Catenin haploinsufficient mice subjected to endurance training displayed a decreased β-catenin transcriptional activity, attenuated cardiomyocytes hypertrophic growth, and enhanced activation of AMP-activated protein kinase (AMPK), phosphoinositide-3-kinase–Akt (Pi3K–Akt), and mitogen-activated protein kinase/extracellular signal-regulated kinases 1/2 (MAPK/Erk1/2) signaling pathways compared to trained wild type mice. We further observed an increased level of proteins involved in glucose aerobic metabolism and β-oxidation along with perturbed activity of mitochondrial oxidative phosphorylation complexes (OXPHOS) in trained β-catenin haploinsufficient mice. Taken together, Wnt/β-catenin signaling appears to govern metabolic regulatory programs, sustaining metabolic plasticity in adult hearts during the adaptation to endurance training.

scholarly journals p38α Mitogen-Activated Protein Kinase Plays a Critical Role in Cardiomyocyte Survival but Not in Cardiac Hypertrophic Growth in Response to Pressure Overload

2004 ◽  
Vol 24 (24) ◽  
pp. 10611-10620 ◽  
Author(s):  
Kazuhiko Nishida ◽  
Osamu Yamaguchi ◽  
Shinichi Hirotani ◽  
Shungo Hikoso ◽  
Yoshiharu Higuchi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cardiac Hypertrophy ◽  
Knockout Mice ◽  
Cardiac Fibrosis ◽  
Critical Role ◽  
Pressure Overload ◽  
Mitogen Activated Protein Kinase ◽  
Hypertrophic Growth ◽  
Mitogen Activated Protein ◽  
Cardiomyocyte Survival

ABSTRACT The molecular mechanism for the transition from cardiac hypertrophy, an adaptive response to biomechanical stress, to heart failure is poorly understood. The mitogen-activated protein kinase p38α is a key component of stress response pathways in various types of cells. In this study, we attempted to explore the in vivo physiological functions of p38α in hearts. First, we generated mice with floxed p38α alleles and crossbred them with mice expressing the Cre recombinase under the control of the α-myosin heavy-chain promoter to obtain cardiac-specific p38α knockout mice. These cardiac-specific p38α knockout mice were born normally, developed to adulthood, were fertile, exhibited a normal life span, and displayed normal global cardiac structure and function. In response to pressure overload to the left ventricle, they developed significant levels of cardiac hypertrophy, as seen in controls, but also developed cardiac dysfunction and heart dilatation. This abnormal response to pressure overload was accompanied by massive cardiac fibrosis and the appearance of apoptotic cardiomyocytes. These results demonstrate that p38α plays a critical role in the cardiomyocyte survival pathway in response to pressure overload, while cardiac hypertrophic growth is unaffected despite its dramatic down-regulation.

Modification of ischemia/reperfusion induced infarct size by ischemic preconditioning in hypertrophied hearts

2021 ◽  
Vol 99 (2) ◽  
pp. 218-223
Author(s):  
Mohamad Nusier ◽  
Mohammad Alqudah ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Protein Kinase ◽  
Cardiac Hypertrophy ◽  
Infarct Size ◽  
P38 Mapk ◽  
Ischemic Preconditioning ◽  
Creatine Phosphokinase ◽  
Ischemia Reperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Normal Heart ◽  
Mitogen Activated Protein

This study examined the effects of ischemic preconditioning (IP) on the ischemia/reperfusion (I/R) induced injury in normal and hypertrophied hearts. Cardiac hypertrophy in rabbits was induced by L-thyroxine (0.5 mg/kg/day for 16 days). Hearts with or without IP (3 cycles of 5 min ischemia and 10 min reperfusion) were subjected to I/R (60 min ischemia followed by 60 min reperfusion). IP reduced the I/R-induced infarct size from 68% to 24% and 57% to 33% in the normal and hypertrophied hearts, respectively. Leakage of creatine phosphokinase in the perfusate from the hypertrophied hearts due to I/R was markedly less than that form the normal hearts; IP prevented these changes. Although IP augmented the increase in phosphorylated p38-mitogen-activated protein kinase (p38-MAPK) content due to I/R, this effect was less in the hypertrophied than in the normal heart. These results suggest that reduced cardioprotection by IP of the I/R-induced injury in hypertrophied hearts may be due to reduced activation of p38-MAPK in comparison with normal hearts.

scholarly journals Effects of Sodium Ferulate on Cardiac Hypertrophy Are via the CaSR-Mediated Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Panpan Chen ◽  
Zhaoqin Wen ◽  
Wanlan Shi ◽  
Zhongli Li ◽  
Xiaoyan Chen ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Cardiovascular Diseases ◽  
Protein Kinase ◽  
Cardiac Hypertrophy ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Myocardial Hypertrophy ◽  
Mitogen Activated Protein Kinase ◽  
Kinase C ◽  
Mitogen Activated Protein

As a common complication of many cardiovascular diseases, cardiac hypertrophy is characterized by increased cardiac cell volume, reorganization of the cytoskeleton, and the reactivation of fetal genes such as cardiac natriuretic peptide and β-myosin heavy chain. Cardiac hypertrophy is a distinguishing feature of some cardiovascular diseases. Our previous study showed that sodium ferulate (SF) alleviates myocardial hypertrophy induced by coarctation of the abdominal aorta, and these protective effects may be related to the inhibition of protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signaling pathways. This study investigated the inhibitory effect and mechanism of SF on myocardial hypertrophy in spontaneously hypertensive rats (SHRs). The effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement, pathological analysis, and detection of atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC) expression. To investigate the mechanisms underlying the anti-hypertrophic effects of SF, the calcium-sensing receptor (CaSR), calcineurin (CaN), nuclear factor of activated T cells 3 (NFAT3), zinc finger transcription factor 4 (GATA4), protein kinase C beta (PKC-β), Raf-1, extracellular signal-regulated kinase 1/2 (ERK 1/2), and mitogen-activated protein kinase phosphatase-1 (MKP-1) were detected by molecular biology techniques. Treatment with SF ameliorated myocardial hypertrophy in 26-week-old SHRs. In addition, it downregulated the levels of ANP, β-MHC, CaSR, CaN, NFAT3, phosphorylated GATA4 (p-GATA4), PKC-β, Raf-1, and p-ERK 1/2; and upregulated the levels of p-NFAT3 and MKP-1. These results suggest that the effects of SF on cardiac hypertrophy are related to regulation of the CaSR-mediated signaling pathway.

scholarly journals Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs) by the G-protein-coupled receptor agonist phenylephrine in the perfused rat heart

1998 ◽  
Vol 332 (2) ◽  
pp. 459-465 ◽  
Author(s):  
Antigone LAZOU ◽  
Peter H. SUGDEN ◽  
Angela CLERK
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
P38 Mapk ◽  
Mitogen Activated Protein Kinase ◽  
Hypertrophic Growth ◽  
Mitogen Activated Protein ◽  
Powerful Activator ◽  
P38 Mapk Inhibitor ◽  
Cellular Stresses ◽  
P38 Mapks

We investigated the ability of phenylephrine (PE), an α-adrenergic agonist and promoter of hypertrophic growth in the ventricular myocyte, to activate the three best-characterized mitogen-activated protein kinase (MAPK) subfamilies, namely p38-MAPKs, SAPKs/JNKs (i.e. stress-activated protein kinases/c-Jun N-terminal kinases) and ERKs (extracellularly responsive kinases), in perfused contracting rat hearts. Perfusion of hearts with 100 µM PE caused a rapid (maximal at 10 min) 12-fold activation of two p38-MAPK isoforms, as measured by subsequent phosphorylation of a p38-MAPK substrate, recombinant MAPK-activated protein kinase 2 (MAPKAPK2). This activation coincided with phosphorylation of p38-MAPK. Endogenous MAPKAPK2 was activated 4–5-fold in these perfusions and this was inhibited completely by the p38-MAPK inhibitor, SB203580 (10 µM). Activation of p38-MAPK and MAPKAPK2 was also detected in non-contracting hearts perfused with PE, indicating that the effects were not dependent on the positive inotropic/chronotropic properties of the agonist. Although SAPKs/JNKs were also rapidly activated, the activation (2–3-fold) was less than that of p38-MAPK. The ERKs were activated by perfusion with PE and the activation was at least 50% of that seen with 1 µM PMA, the most powerful activator of the ERKs yet identified in cardiac myocytes. These results indicate that, in addition to the ERKs, two MAPK subfamilies, whose activation is more usually associated with cellular stresses, are activated by the Gq/11-protein-coupled receptor (Gq/11PCR) agonist, PE, in whole hearts. These data indicate that Gq/11PCR agonists activate multiple MAPK signalling pathways in the heart, all of which may contribute to the overall response (e.g. the development of the hypertrophic phenotype).

Molecular responses to high-intensity interval exerciseThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 428-432 ◽  
Author(s):  
Martin Gibala
Keyword(s):  
Protein Kinase ◽  
Endurance Training ◽  
Signaling Pathways ◽  
Mitochondrial Biogenesis ◽  
High Intensity ◽  
Mitogen Activated Protein Kinase ◽  
Interval Exercise ◽  
Mitogen Activated Protein ◽  
High Intensity Interval ◽  
Amp Activated Protein Kinase

From a cell-signaling perspective, short-duration intense muscular work is typically associated with resistance training and linked to pathways that stimulate growth. However, brief repeated sessions of high-intensity interval exercise training (HIT) induce rapid phenotypic changes that resemble traditional endurance training. Given the oxidative phenotype that is rapidly upregulated by HIT, it is plausible that metabolic adaptations to this type of exercise could be mediated in part through signaling pathways normally associated with endurance training. A key controller of oxidative enzyme expression in skeletal muscle is peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional coactivator that serves to coordinate mitochondrial biogenesis. Most studies of acute PGC-1α regulation in humans have used very prolonged exercise interventions; however, it was recently shown that a surprisingly small dose of very intense interval exercise, equivalent to only 2 min of all-out cycling, was sufficient to increase PGC-1α mRNA during recovery. Intense interval exercise has also been shown to acutely increase the activity of signaling pathways linked to PGC-1α and mitochondrial biogenesis, including AMP-activated protein kinase (α1 and α2 subunits) and the p38 mitogen-activated protein kinase. In contrast, signaling pathways linked to muscle growth, including protein kinase B/Akt and downstream targets p70 ribosomal S6 kinase and 4E binding protein 1, are generally unchanged after acute interval exercise. Signaling through AMP-activated protein kinase and p38 mitogen-activated protein kinase to PGC-1α may therefore explain, in part, the metabolic remodeling induced by HIT, including mitochondrial biogenesis and an increased capacity for glucose and fatty acid oxidation.

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