A5004739337- Muscle Physiology and Disorders
- Exercise and Physiological Responses
- Adipose Tissue and Metabolism
- Muscle activation and electromyography studies
- Cardiomyopathy and Myosin Studies
- Tissue Engineering and Regenerative Medicine
- Cellular Mechanics and Interactions
- Calpain Protease Function and Regulation
- Cell Adhesion Molecules Research
- Neurogenetic and Muscular Disorders Research
- Muscle metabolism and nutrition
- Sports injuries and prevention
- Genetic Neurodegenerative Diseases
- Mesenchymal stem cell research
- Nutrition and Health in Aging
- Extracellular vesicles in disease
- Genetic Syndromes and Imprinting
- Advanced Sensor and Energy Harvesting Materials
- Coral and Marine Ecosystems Studies
- Spaceflight effects on biology
- Marine Invertebrate Physiology and Ecology
- Parathyroid Disorders and Treatments
- Ion channel regulation and function
- Tendon Structure and Treatment
- Cardiovascular and exercise physiology
University of California, Los Angeles
2016-2025
University of California System
2013
Laboratoire d’immunologie intégrative du cancer
2008-2012
Department of Physiological Sciences
1996-2009
UCLA Health
2005-2007
University of Regensburg
2007
National Institutes of Health
2002
American Physiological Society
1997
The University of Texas Southwestern Medical Center
1996
University of Puget Sound
1994
Dystrophin-deficient muscles experience large reductions in expression of nitric oxide synthase (NOS), which suggests that NO deficiency may influence the dystrophic pathology. Because can function as an antiinflammatory and cytoprotective molecule, we propose loss NOS from muscle exacerbates inflammation fiber damage by inflammatory cells. Analysis transgenic mdx mice were null mutants for dystrophin, but expressed normal levels muscle, showed normalization production caused macrophage...
Duchenne muscular dystrophy (DMD) is the most common, lethal, muscle-wasting disease of childhood. Previous investigations have shown that muscle macrophages may play an important role in promoting pathology mdx mouse model DMD. In present study, we investigate mechanism through which promote and assess whether phenotype changes between stage peak necrosis (4 weeks age) regeneration (12 weeks). We find 4-week-old muscles contain a population pro-inflammatory, classically activated M1 lyse...
Abstract We examined the function of IL-10 in regulating changes macrophage phenotype during muscle growth and regeneration following injury. Our findings showed that Th1 cytokine response inflamed is characterized by high levels expression CD68, CCL-2, TNF-α, IL-6 at 1 d postinjury. During transition to Th2 response, those transcripts declined, whereas CD163, IL-10, IL-10R1, arginase-1 increased. Ablation amplified postinjury, causing increases CCL2, while preventing a subsequent increase...
Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder associated with dystrophin deficiency that results in chronic inflammation and severe skeletal muscle degeneration. In DMD mouse models patients, we find IkappaB kinase/NF-kappaB (IKK/NF-kappaB) signaling persistently elevated immune cells regenerative fibers. Ablation of 1 allele the p65 subunit NF-kappaB was sufficient to improve pathology mdx mice, model DMD. addition, conditional deletion IKKbeta mice elucidated functions...
Muscle injury or modified muscle use can stimulate invasion by leucocytes that have the potential to increase tissue damage promote growth and repair. In present investigation, we examined role of macrophages in injury, repair regeneration during loading. Weight-bearing was removed from hindlimbs mice for 10 days followed reloading through normal ambulation. During unloading period, soleus fibre cross-section decreased 38%. Prior onset reloading, received a series intraperitoneal injections...
M1 macrophages play a major role in worsening muscle injury the mdx mouse model of Duchenne muscular dystrophy. However, also contains M2c that can promote tissue repair, indicating factors regulating balance between and phenotypes could influence severity disease. Because interleukin-10 (IL-10) modulates macrophage activation vitro its expression is elevated muscles, we tested whether IL-10 influenced phenotype changes affected pathology Ablation mice increased damage vivo reduced strength....
Regulatory T cells ameliorate symptoms of muscular dystrophy by suppressing type 1 inflammatory responses in muscle.
Neuronal nitric oxide synthase (nNOS) in fast-twitch skeletal muscle fibers is primarily particulate contrast to its greater solubility brain. Immunohistochemistry shows nNOS localized the sarcolemma, with enrichment at force transmitting sites, myotendinous junctions, and costameres. Because this distribution similar dystrophin, we determined if expression was affected by loss of dystrophin. Significant immunoreactivity enzyme activity absent tissues from patients Duchenne muscular...
The hypothesis that distinct populations of macrophages are associated with muscle necrosis and regeneration was examined in Wistar rat soleus after 10 days hindlimb suspension 2, 4, 7 the resumption weight bearing. Necrosis identified using histological features, such as fiber infiltration, immunohistochemical techniques for developmental myosin heavy chain (dMHC). Light-microscopic observations show necrotic fibers 2-day reloaded were invaded by ED1+ Ia+ macrophages. number muscles 2...
The hypothesis that changes in muscle activation and loading regulate the expression activity of neuronal nitric oxide (NO) synthase (nNOS) was tested using vitro vivo approaches. Removal weight bearing from rat hindlimb muscles for 10 days resulted a significant decrease nNOS protein mRNA concentration soleus muscles, which returned to control concentrations after return bearing. Similarly, cultured myotubes increased by application cyclic 2 days. NO release excised significantly single...
ABSTRACT The current view that death of dystrophin-deficient muscle fibers is a necrotic process relies primarily upon the histological appearance tissue after degenerative well advanced. Here, we tested this by examining possibility apoptosis component cell death. Three assays for were employed in analyzing prenecrotic, peak and regenerated hindlimb mdx mice: (1) terminal deoxynucleotidyl transferase (TdT) mediated end-labeling DNA nuclei sections; (2) ladders; (3) electron microscopic...
Myostatin, a TGF‐β family member, is negative regulator of muscle growth. Here, we generated transgenic mice that expressed myostatin mutated at its cleavage site under the control specific promoter creating dominant myostatin. These exhibited significant (20–35%) increase in mass resulted from myofiber hypertrophy and not hyperplasia. We also evaluated role degenerative states, such as muscular dystrophy, found downregulation Thus, further inhibition may permit increased growth disorders.
Previous findings have provided strong evidence that myostatin functions as a negative regulator of muscle mass during development and growth. In the present study, we test hypothesis may serve similar function in fully differentiated experiencing modified loading. Our show expression can be modulated differentiated, non-pathological skeletal manner is inversely related to changes mass. Atrophy rat hind limb muscles induced by 10 days unloading resulted 16% decrease plantaris mass, 110%...
Muscle wasting is a prominent feature of several systemic diseases, neurological damage and muscle disuse. The contribution calpain proteases to in any instance injury or disease has remained unknown because the inability specifically perturb activity vivo . We have generated transgenic mouse with muscle‐specific overexpression calpastatin, which endogenous inhibitor calpains, induced atrophy by unloading hindlimb musculature for 10 days. Expression transgene resulted increases calpastatin...
Death of dystrophin-deficient muscle purportedly results from increases in [Ca]in that cause the activation calpains. We have tested whether calpains play a role this process by assaying for changes calpain concentration and peak necrotic mdx mice (4 weeks age) completely regenerated (14 age). Biochemical fractionation immunoblotting with epitope-specific antisera allowed measurement concentrations m- μ-calpains extent autoproteolytic modification. Our findings show total is elevated both...
Muscle aging is associated with changes in myeloid cell phenotype that may influence age-related muscle structure. We tested whether preventing reductions neuronal nitric oxide synthase (nNOS) would obviate cells muscle. Our findings show elevations of anti-inflammatory M2a macrophages can increase fibrosis. Expression a muscle-specific nNOS transgene mice prevented increases macrophages. Transgene expression also reduced collagens and decreased The arginase-1 but did not TGFβ expression,...
Junctions formed by skeletal muscles where they adhere to tendons, called myotendinous junctions, are sites of tight adhesion and forces generated the cell placed on substratum. In this regard, junctions focal contacts fibroblasts in vitro analogues. Talin is a protein located at that may be involved force transmission from actin filaments plasma membrane. This study investigates whether talin also found junctions. Protein separations SDS polyacrylamide gels immunolabeling procedures show...