Muscle Cell News Volume 4.24 | Jul 15 2019

TOP STORY

Reassessment of c-Kit⁺ Cells for Cardiomyocyte Contribution in Adult Heart

Researchers generated two new Kit-Cre drivers that labeled all Kit⁺ cells efficiently without removing the endogenous Kit gene. New fate-mapping data showed that Kit⁺ cardiac stem cells did not contribute to de novo cardiomyocytes during cardiac homeostasis or after injury. [Circulation] Full Article

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Cardiomyocyte Orientation Modulated by the Numb Family Proteins–N-Cadherin Axis Is Essential for Ventricular Wall Morphogenesis

To determine how Numb regulated N-cadherin membrane localization, the authors generated an mCherry:Numb knockin line and found that Numb localized to diverse endocytic organelles but mainly to the recycling endosome. Consistent with this localization, cardiomyocytes in myocardial-specific Numb and Numblike double-knockout hearts did not display defects in N-cadherin internalization but rather in postendocytic recycling to the plasma membrane. [Proc Natl Acad Sci USA] Full Article

Pseudo-Bipolar Spindle Formation and Cell Division in Postnatal Binucleated Cardiomyocytes

Postnatal rat binucleated cardiomyocytes were stimulated to re-enter the cell cycle either by fetal bovine serum or a combination of fibroblast growth factor 1 and p38 MAP kinase inhibitor. Phase-contrast videos revealed that binucleated cardiomyocytes formed one metaphase plate and preferentially underwent afterwards cytokinesis failure. [J Mol Cell Cardiol] Abstract | Graphical Abstract

TRPC3-Nox2 Axis Mediates Nutritional Deficiency-Induced Cardiomyocyte Atrophy

Investigators report that ATP induced atrophy of neonatal rat cardiomyocytes without cell death through P2Y₂ receptors. ATP led to overproduction of reactive oxygen species through an increased amount of NADPH oxidase (Nox) 2 proteins, due to increased physical interaction between Nox2 and canonical transient receptor potential 3 (TRPC3). [Sci Rep] Full Article

Inhibition of miR-181b-5p Protects Cardiomyocytes against Ischemia/Reperfusion Injury by Targeting AKT3 and PI3KR3

Data indicated that miR-181b-5p negatively regulated the expression of AKT3 and PIK3R3 through directly binding with its 3′-untranslated region. The study indicated that miR-181b-5p was essential for myocardial ischemia/reperfusion injury via regulation of PI3K/Akt signaling pathway and could be a potential therapeutic target in ischemic heart disease. [J Cell Biochem] Abstract

SKELETAL MUSCLE CELLS

Peroxisome Proliferator-Activated Receptor γ Coactivator 1α Regulates Mitochondrial Calcium Homeostasis, Sarcoplasmic Reticulum Stress, and Cell Death to Mitigate Skeletal Muscle Aging

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) prevented tubular aggregate formation and cell death pathway activation in old muscle. Similarly, the pro-apoptotic effects of ceramide and thapsigargin were blunted by PGC-1α in muscle cells. [Aging Cell] Full Article

A Novel Mitochondrial Micropeptide MPM Enhances Mitochondrial Respiratory Activity and Promotes Myogenic Differentiation

Scientists identified a novel muscle-enriched micropeptide that was localized to mitochondria (named MPM, micropeptide in mitochondria) and upregulated during in vitro differentiation of C2C12 myoblasts and in vivo early postnatal skeletal muscle development, and muscle regeneration after cardiotoxin damage. Downregulation of MPM was observed in the muscular tissues of tibial muscular dystrophy and Duchenne muscular dystrophy patients. [Cell Death Dis] Full Article

A Muscle-Specific UBE2O/AMPKα2 Axis Promotes Insulin Resistance and Metabolic Syndrome in Obesity

Through phenotype analysis of high-fat diet-induced mice with muscle-, fat-, or liver-specific knockout of ubiquitin-conjugating enzyme E2O (Ube2o), researchers identified UBE2O as an essential regulator of glucose and lipid metabolism programs in skeletal muscle, but not in adipose or liver tissue. Mechanistically, UBE2O acted as a ubiquitin ligase and targeted AMPKα2 for ubiquitin-dependent degradation in skeletal muscle; further, muscle-specific heterozygous knockout of Prkaa2 ablated UBE2O-controlled metabolic processes. [JCI Insight] Full Article | Graphical Abstract

SMOOTH MUSCLE CELLS

Smooth Muscle-Specific TMEM16A Expression Protects against Angiotensin II-Induced Cerebrovascular Remodeling via Suppressing Extracellular Matrix Deposition

Researchers generated a transgenic mouse that overexpresses TMEM16A specifically in vascular smooth muscle cells. They observed that vascular remodeling in the basilar artery during angiotensin II-induced hypertension was significantly suppressed upon vascular smooth muscle-specific overexpression of TMEM16A relative to control mice. [J Mol Cell Cardiol] Abstract

Elastolytic Activity of Cysteine Cathepsins K, S, and v Promotes Vascular Calcification

Cathepsin-generated elastin peptides increased the calcification of MOVAS-1 cells acting through the ERK1/2 pathway by 34–36%. Scientists made similar observations when cathepsin-generated elastin peptides were added to ex vivo mouse aorta rings. [Sci Rep] Full Article

Drug Eluting Stent Specifically Designed to Target Vascular Smooth Muscle Cell Phenotypic Modulation Attenuated Restenosis through YAP Pathway

Vascular smooth muscle cell (SMC) contractile protein from freshly isolated rat aorta was expressed at a high level, but its expression was dramatically reduced after SMCs were cultured in 10% FBS for one week. After sorafenib treatment, SMC contractile protein expression was markedly up-regulated. [Am J Physiol Heart Circ Physiol] Abstract

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Autophagy, Apoptosis, and Mitochondria: Molecular Integration and Physiological Relevance in Skeletal Muscle

Although both autophagic and apoptotic signaling are active in skeletal muscle during various diseases and atrophy, their specific roles here are somewhat unique. Given biology’s growing understanding of how specific changes at the cellular level impact whole-organism physiology, there is an equally growing interest in pharmacological manipulation of apoptosis and/or autophagy for altering human physiology and health. [Am J Physiol Cell Physiol] Abstract

Cardiomyopathy Associated with Diabetes: The Central Role of the Cardiomyocyte

The term diabetic cardiomyopathy (DCM) labels an abnormal cardiac structure and performance due to intrinsic heart muscle malfunction, independently of other vascular co-morbidity. DCM, accounting for 50%-80% of deaths in diabetic patients, represents a worldwide problem for human health and related economics. [Int J Mol Sci] Full Article

Visit our reviews page to see a complete list of reviews in the muscle cell research field.

Cytokinetics Announces Completion of Enrollment in Galactic-Hf, Phase III Clinical Trial of Omecamtiv Mecarbil in Patients with Heart Failure

Cytokinetics, Incorporated announced the completion of patient enrollment in Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF), the Phase III event driven cardiovascular outcomes clinical trial of omecamtiv mecarbil which is being conducted by Amgen, in collaboration with Cytokinetics. [Cytokinetics, Incorporated] Press Release

Orion Completes Enrollment in the REFALS Phase III Trial Studying the Effect of Oral Levosimendan in Patients with Amyotrophic Lateral Sclerosis (ALS)

Orion Corporation announced the completion of patient enrollment in the Phase III REFALS trial, studying the effects of oral levosimendan on respiratory function in patients with ALS. [Orion Corporation] Press Release

Capricor Therapeutics Announces Positive Results from Its Interim Analysis in the HOPE-2 Trial to Treat Patients with Duchenne Muscular Dystrophy

Capricor Therapeutics, Inc. announced that a pre-specified interim analysis performed on six-month data from the HOPE-2 trial showed statistically significant results across several independent clinical measures. [Capricor Therapeutics, Inc] Press Release

Cambridge Heart and Lung Research Institute Receives Major Funding Boost

Chris Skidmore, Minister for Universities, Science, Research and Innovation, announced on 10 July 2019 a £30 million award to the University of Cambridge to support the new Cambridge Heart and Lung Research Institute. The Institute will draw together the highest concentration of heart and lung researchers from academia, healthcare and industry in Europe. [The University of Cambridge] Press Release

University of California Loses Access to New Journal Articles Published by Elsevier after Research Access Fight

Researchers in the University of California system lost subscription access to the major publisher Elsevier, the result of a closely watched fight between the two parties over how academic research should get read and paid for. [STAT News] Editorial

Sweden Passes Law For National Research Misconduct Agency

After several high-profile cases, the country’s government is creating a board to oversee and investigate all serious allegations of scientific misconduct. [The Scientist] Editorial

As Visa Difficulties Persist, Scientists Push for Change

Individual researchers and science societies are finding solutions so colleagues around the globe can attend conferences, from remote presentations to relocating conferences. [The Scientist] Editorial

NEW 2019 Muscle Study Group (MSG) Annaul Scientific Meeting
September 20-22, 2019
Snowbird, Utah, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellowship – Molecular Mechanisms of Atrial Fibrillation (Electrophysiology and Heart Modeling Institute)

Technical Director – Stem Cell and Genomic Engineering (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Cardiovascular Biology (Oklahoma Medical Research Foundation)

Research Scientist – Cellular Electrophysiology (Duke University)

Research Fellow – Sequencing and Functional Genomics in Cardiovascular Biology (The University of Cambridge)

Postdoctoral Researcher – Muscle Atrophy and Metabolism (McGill University)

Postdoctoral Researchers – Cardiovascular Studies (Virginia Tech)

Postdoctoral – Proteomics of Muscles and Aging (Oklahoma Medical Research Foundation)

Postdoctoral Fellow – Facioscapulohumeral Muscular Dystrophy Research (Pfizer)

Postdoctoral Fellow – Cardiac and Skeletal Muscle Engineering (Georgia Institute of Technology & Emory University School of Medicine)

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