A5059391915- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Cardiovascular Function and Risk Factors
- Signaling Pathways in Disease
- Peptidase Inhibition and Analysis
- Cardiac electrophysiology and arrhythmias
- RNA Research and Splicing
- Force Microscopy Techniques and Applications
- Ion channel regulation and function
- Cardiac Fibrosis and Remodeling
- Integrated Circuits and Semiconductor Failure Analysis
- Viral Infections and Immunology Research
- Genetic Neurodegenerative Diseases
- Muscle Physiology and Disorders
- Cell Adhesion Molecules Research
- RNA and protein synthesis mechanisms
- Studies on Chitinases and Chitosanases
- Cardiovascular and exercise physiology
- Blood disorders and treatments
- Molecular Biology Techniques and Applications
- Empathy and Medical Education
- Electron and X-Ray Spectroscopy Techniques
- Cardiac Ischemia and Reperfusion
- Metabolism, Diabetes, and Cancer
- Neurogenetic and Muscular Disorders Research
The Ohio State University
2015-2024
Lung Institute
2014-2023
The Ohio State University Wexner Medical Center
2021
Recent studies suggest that proarrhythmic effects of cardiac glycosides (CGs) on cardiomyocyte Ca2+ handling involve generation reactive oxygen species (ROS). However, the specific pathway(s) ROS production and subsequent downstream molecular events mediate CG-dependent arrhythmogenesis remain to be defined. We examined digitoxin (DGT) in cardiomyocytes using a combination pharmacological approaches genetic mouse models. Myocytes isolated from mice deficient NADPH oxidase type 2 (NOX2KO)...
Phosphorylation and acetylation of sarcomeric proteins are important for fine-tuning myocardial contractility. Here, we used bottom-up proteomics label-free quantification to identify novel post-translational modifications (PTMs) on β-myosin heavy chain (β-MHC) in normal failing human heart tissues. We report six acetylated lysines two phosphorylated residues: K34-Ac, K58-Ac, S210-P, K213-Ac, T215-P, K429-Ac, K951-Ac, K1195-Ac. K951-Ac was significantly reduced both ischemic nonischemic...
Troponin I (TnI) is a major regulator of cardiac muscle contraction and relaxation. During physiological pathological stress, TnI differentially phosphorylated at multiple residues through different signaling pathways to match function demand. The combination these phosphorylations can exhibit an expected or unexpected functional integration, whereby the two are than that predicted from combined each individual phosphorylation alone. We have shown Ser-23/24 Ser-150 integration simultaneously...
This study measured how heart failure affects the contractile properties of human myocardium from left and right ventricles. The data showed that maximum force power were reduced by approximately 30% in multicellular preparations both ventricles, possibly because ventricular remodeling (e.g., cellular disarray and/or excess fibrosis). Heart increased calcium (Ca2+) sensitivity contraction but effect was bigger samples. changes Ca2+ associated with ventricle-specific phosphorylation troponin...
A healthy heart is able to modify its function and increase relaxation through post-translational modifications of myofilament proteins. While there are known examples serine/threonine kinases directly phosphorylating proteins function, the roles tyrosine (Y) phosphorylation have not been demonstrated. The protein TnI (troponin I) inhibitory subunit troponin complex a key regulator cardiac contraction relaxation. We previously demonstrated that TnI-Y26 decreases calcium-sensitive force...
Heart failure with systolic dysfunction is characterized by insufficient contractility. Standards of care for heart treat symptoms, however there are currently no approved therapies to increase contractility directly improve the ability pump blood. Previously tested positive inotropes increased function through mechanisms that intracellular calcium. Unfortunately, these early were associated detrimental effects and worsened outcomes therefore not long-term use. There remains a need an...
With an increase in the body's metabolic demand (e.g., exercise), heart must its pumping performance. To achieve this increased performance, relies on cardiac reserve, which is ability to systolic and diastolic function. The mechanism responsible for reserve poorly understood. myofilaments are essential contraction/relaxation, with troponin I (the inhibitory subunit of troponin, TnI) being a key regulatory protein. Studies have shown that TnI serine 23/24 (S23/S24) phosphorylation...
The troponin (Tn) complex is a critical regulatory and integrative hub for myofilament post-translational modifications that regulate cardiac contraction. Beta-adrenergic-induced protein kinase A (PKA) phosphorylation of I (cTnI) at Ser-23/24 major contractile modulator. In addition to this PKA-induced phosphorylation, cTnI can be simultaneously phosphorylated number other residues. To fully understand the molecular mechanisms underlie muscle regulation level, phosphorylations must studied...
Heart failure results in depressed contraction and slowed relaxation, both of which limit heart function contribute to the progression disease. Currently there is no chronic therapy accelerate relaxation reverse diastolic dysfunction present failure. Myocardial regulated by serine/threonine phosphorylation key regulatory proteins. Tyrosine (Tyr) specific kinases are expressed but Tyr proteins modulate has not been demonstrated. To investigate effects kinase on cardiac we employed a novel...