Abstract

Mechanical perturbations of myotubes in cultures will be performed by deformation of a flexible substrate, and on rat hind limbs by suspension and reloading. The NOS-dependent responses that will be assayed include changes in expression of structural proteins enriched at MTJs (talin) or regulatory proteins that are enriched at MTJs (NOS). NOS dependence of early genes in response to modified muscle loading will also be tested as will NO-mediated regulation of calcium-dependent proteases that are enriched at MTJs. The specific mechanism by which NO covalently modifies skeletal muscle actin will be examined. Hind limb immobilization at shortened length followed by remobilization will be used to examine the effect of inhibition of NOS on sarcomere addition.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR040343-10
Application #
2899859
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Lymn, Richard W
Project Start
1989-08-05
Project End
2002-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Curzi, D; Lattanzi, D; Ciuffoli, S et al. (2013) Growth hormone plus resistance exercise attenuate structural changes in rat myotendinous junctions resulting from chronic unloading. Eur J Histochem 57:e37
Wehling-Henricks, Michelle; Tidball, James G (2011) Neuronal nitric oxide synthase-rescue of dystrophin/utrophin double knockout mice does not require nNOS localization to the cell membrane. PLoS One 6:e25071
Villalta, S Armando; Rinaldi, Chiara; Deng, Bo et al. (2011) Interleukin-10 reduces the pathology of mdx muscular dystrophy by deactivating M1 macrophages and modulating macrophage phenotype. Hum Mol Genet 20:790-805
Wehling-Henricks, Michelle; Jordan, Maria C; Gotoh, Tomomi et al. (2010) Arginine metabolism by macrophages promotes cardiac and muscle fibrosis in mdx muscular dystrophy. PLoS One 5:e10763
Villalta, S Armando; Nguyen, Hal X; Deng, Bo et al. (2009) Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy. Hum Mol Genet 18:482-96
Wehling-Henricks, Michelle; Oltmann, Meredith; Rinaldi, Chiara et al. (2009) Loss of positive allosteric interactions between neuronal nitric oxide synthase and phosphofructokinase contributes to defects in glycolysis and increased fatigability in muscular dystrophy. Hum Mol Genet 18:3439-51
Wehling-Henricks, Michelle; Sokolow, Sophie; Lee, Jamie J et al. (2008) Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophy. Hum Mol Genet 17:2280-92
Tidball, James G; Wehling-Henricks, Michelle (2005) Damage and inflammation in muscular dystrophy: potential implications and relationships with autoimmune myositis. Curr Opin Rheumatol 17:707-13
Wehling-Henricks, Michelle; Jordan, Maria C; Roos, Kenneth P et al. (2005) Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium. Hum Mol Genet 14:1921-33
Tidball, James G; Wehling-Henricks, Michelle (2004) Expression of a NOS transgene in dystrophin-deficient muscle reduces muscle membrane damage without increasing the expression of membrane-associated cytoskeletal proteins. Mol Genet Metab 82:312-20

Showing the most recent 10 out of 51 publications