A5027345742- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Muscle metabolism and nutrition
- Muscle activation and electromyography studies
- Exercise and Physiological Responses
- Ubiquitin and proteasome pathways
- Cardiomyopathy and Myosin Studies
- Genetic Neurodegenerative Diseases
- Spaceflight effects on biology
- Neurogenetic and Muscular Disorders Research
- Sports Performance and Training
- Mitochondrial Function and Pathology
- Transcranial Magnetic Stimulation Studies
- Nerve injury and regeneration
- Nutrition and Health in Aging
- Genetics and Physical Performance
- Cerebral Palsy and Movement Disorders
- Pain Mechanisms and Treatments
- Spinal Cord Injury Research
- Autophagy in Disease and Therapy
- Botulinum Toxin and Related Neurological Disorders
- Cardiovascular and exercise physiology
- Hormonal and reproductive studies
- Diet and metabolism studies
- Birth, Development, and Health
Fraternal Order of Eagles
2019-2025
University of Iowa
2016-2025
University of California, Davis
2012-2024
Oklahoma Medical Research Foundation
2023-2024
Oklahoma City VA Medical Center
2023-2024
University of Oxford
2023
Iowa City VA Health Care System
2023
Veterans Health Administration
2023
VA Northern California Health Care System
2014-2019
San Francisco VA Medical Center
2019
Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of atrophy, we performed transcript profiling. Although many genes were up-regulated a single rat model only small subset was universal all atrophy models. Two these encode ubiquitin ligases: Muscle RING Finger 1 ( MuRF1 ), gene designate Atrophy F-box MAFbx the latter being member SCF family E3 ligases. Overexpression myotubes produced whereas mice deficient either or...
The muscle specific ubiquitin E3 ligase MuRF1 has been implicated as a key regulator of atrophy under variety conditions, such during synthetic glucocorticoid treatment. FOXO class transcription factors have proposed important regulators expression, but its regulation by glucocorticoids is not well understood. promoter contains near-perfect palindromic response element (GRE) 200 base pairs upstream the start site. GRE highly conserved in mouse, rat, and human genes along with directly...
Age-related loss of muscle mass and strength can be accelerated by impaired recovery following a transient atrophic stimulus. The aim this study was to identify the mechanisms underlying attenuated in old rats disuse-induced atrophy. Adult (9 month) (29 male F344BN underwent hindlimb unloading (HU) followed reloading. HU induced significant atrophy muscles both adult (17-38%) (8-29%) rats, but only exhibited full upon Upon reloading, total RNA protein synthesis increased similar extent...
Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood
We have investigated the effects of insulin, amino acids, and degree muscle loading on phosphorylation Ser2448, a site in mammalian target rapamycin (mTOR) phosphorylated by protein kinase B (PKB)in vitro. Phosphorylation was assessed immunoblotting with phosphospecific antibody (anti-Ser(P)2448) mTAb1, an activating whose binding is inhibited region mTOR that contains Ser2448. Incubating rat diaphragm muscles insulin increased Ser2448 but did not change total amount mTOR. Insulin, activated...
Increasing the mechanical load on skeletal muscle results in increased expression of insulin-like growth factor I (IGF-I), which is thought to be a critical step induction hypertrophy. To determine role IGF-I receptor load-induced hypertrophy, we utilized transgenic mouse model (MKR) that expresses dominant negative specifically muscle. Skeletal hypertrophy was induced plantaris using functional overload (FO) model, has previously been shown induce significant elevations Adult male wild-type...
Skeletal muscle atrophy occurs under a variety of conditions and can result from alterations in both protein synthesis degradation. The muscle-specific E3 ubiquitin ligases, MuRF1 MAFbx, are excellent markers increase divergent atrophy-inducing such as denervation glucocorticoid treatment. While deletion or MAFbx has been reported to spare mass following 14 days denervation, their role other is unclear. goal this study was determine whether attenuates after 2 weeks treatment with the...
Neural activity actively regulates muscle gene expression. This regulation is crucial for specifying functionality and synaptic protein How neural relayed into nuclei connected to the transcriptional machinery, however, not known. Here we identify histone deacetylase HDAC4 as critical linker connecting transcription. We found that normally concentrated at neuromuscular junction (NMJ), where nerve innervates muscle. Remarkably, reduced input by surgical denervation or diseases dissociates...
Clenbuterol and other beta2-adrenergic agonists are effective at inducing muscle growth attenuating atrophy through unknown mechanisms. This study tested the hypothesis that clenbuterol-induced sparing is mediated activation of Akt mammalian target rapamycin (mTOR) signaling pathways. was administered to normal weight-bearing adult rats examine growth-inducing effects undergoing as result hindlimb suspension or denervation muscle-sparing effects. The pharmacological inhibitor in combination...
In 11 tibialis anterior muscles of the cat, a single motor unit was characterized physiologically and subsequently depleted its glycogen through repetitive stimulation an isolated ventral root filament. Muscle cross sections were stained for using periodic acid-Schiff reaction, single-fiber optical densities determined to identify those fibers belonging stimulated unit. Innervation ratios by counting total number muscle in taken several levels muscle. The average innervation fast,...
Key points Ribosome biogenesis is the primary determinant of translational capacity, but its regulation in skeletal muscle following acute resistance exercise poorly understood. Resistance increases protein synthesis acutely, and mass with training, role capacity these processes unclear. Here, we show that activated pathways controlling activity through both rapamycin‐sensitive ‐insensitive mechanisms. Transcription factor c‐Myc downstream targets, which are known to regulate ribosome other...
Deletion of muscle RING finger 1 (MuRF1), an E3 ubiquitin ligase, leads to sparing mass following denervation. The purpose this study was test the hypothesis that in mice with a deletion MuRF1 is due selective inhibition proteasome system. Activities 20S and 26S proteasomes, calpain cathepsin L, were measured triceps surae muscles wild-type (WT) MuRF1-knockout (KO) at 3 14 d In addition, fractional protein synthesis rates differential gene expression WT KO muscle. major finding activities...
Glucocorticoids (GCs) are important regulators of skeletal muscle mass, and prolonged exposure will induce significant atrophy. To better understand the mechanism atrophy induced by elevated GC levels, we examined three different models: exogenous synthetic treatment [dexamethasone (DEX)], nutritional deprivation, denervation. Specifically, tested direct contribution glucocorticoid receptor (GR) in creating a muscle-specific GR-knockout mouse line (MGR e3 KO) using Cre-lox technology. In MGR...
Age-related loss of muscle mass occurs to varying degrees in all individuals and has a detrimental effect on morbidity mortality. Muscle RING Finger 1 (MuRF1), muscle-specific E3 ubiquitin ligase, is believed mediate atrophy through the proteasome system (UPS). Deletion MuRF1 (KO) mice attenuates following denervation, disuse, glucocorticoid treatment; however, its role age-related unknown. In this study, skeletal from male wild-type (WT) KO was studied up age 24 months. fiber...
Disuse is a potent inducer of muscle atrophy, but the molecular mechanisms driving this loss mass are highly debated. In particular, extent to which disuse triggers decreases in protein synthesis or increases degradation, and whether these changes uniform across muscles influenced by age, unclear. We aimed determine impact on degradation lower limb varied function fiber type adult old rats. Alterations were measured soleus, medial gastrocnemius, tibialis anterior (TA) rats subjected hindlimb...