Previous studies have provided some evidence to suggest that the different types of myosin present in skeletal muscle can be modified enzymatically by repeated bouts of physical activity. To date, however, no studies have been designed to adequately test the hypothesis that the myosin isozyme pattern of a given muscle can be regulated in accordance with the functional demands of gaiting speed and of force imposed on it during repeated conventional exercise (running). We propose to test this hypothesis by using a normal animal modeland an overload model in which the medial gastrocnemius and rectus femoris muscles are surgically isolated to be primarily responsible for muscle activity involving the hindlimb musculature. This intervention will limit the total number of fast-twitcha nd slow-twitch motor units participating in locomotion, thereby forcing any potential adaptation to become highly focused. After 8 weeks of surgical induced overload, the overloaded animals, along with normal controls, will be subjected to identicle chronic exercise programs in which the variables of (1) speed and (2) incline or weight addition to animals will be selectively changed. some animals will be instrumented for electromyographic recordings to monitor the relative activation of the muscles during locomotion. At the termination of a given exercise program, the nuscles will be analyzed for: (1) contractile and fatigue properties; (2) Ca++ regulated myofibril ATPase; (3) histochemistry to assess fiber-typing; (4) citrate synthase activity; and (5) myosin analyses consisting of ATPase (including alkaline and acid inactivation), light chain electrophoretic patterns, and native myosin electrophoresis to identify specific fast and slow isozymes. With this combination of exercise models, we should be able to assess how physiological stimuli alter the genetic expression of skeletal muscle in terms of contractile function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR030346-09
Application #
3155773
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1982-07-01
Project End
1993-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Pandorf, Clay E; Jiang, Weihua; Qin, Anqi X et al. (2012) Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle. Am J Physiol Regul Integr Comp Physiol 302:R854-67
Haddad, Fadia; Baldwin, Kenneth M (2010) Reverse transcription of the ribonucleic acid: the first step in RT-PCR assay. Methods Mol Biol 630:261-70
Baldwin, Kenneth M; Haddad, Fadia (2010) Research in the exercise sciences: where we are and where do we go from here--Part II. Exerc Sport Sci Rev 38:42-50
Pandorf, Clay E; Jiang, Weihua H; Qin, Anqi X et al. (2009) Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle. Am J Physiol Regul Integr Comp Physiol 297:R1037-48
McCall, Gary E; Haddad, Fadia; Roy, Roland R et al. (2009) Transcriptional regulation of the myosin heavy chain IIb gene in inactive rat soleus. Muscle Nerve 40:411-9
Pandorf, Clay E; Haddad, Fadia; Wright, Carola et al. (2009) Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading. Am J Physiol Cell Physiol 297:C6-16
Giger, Julia M; Bodell, Paul W; Zeng, Ming et al. (2009) Rapid muscle atrophy response to unloading: pretranslational processes involving MHC and actin. J Appl Physiol (1985) 107:1204-12
Rinaldi, Chiara; Haddad, Fadia; Bodell, Paul W et al. (2008) Intergenic bidirectional promoter and cooperative regulation of the IIx and IIb MHC genes in fast skeletal muscle. Am J Physiol Regul Integr Comp Physiol 295:R208-18
Haddad, Fadia; Qin, Anqi X; Giger, Julie M et al. (2007) Potential pitfalls in the accuracy of analysis of natural sense-antisense RNA pairs by reverse transcription-PCR. BMC Biotechnol 7:21
Mozaffar, Tahseen; Haddad, Fadia; Zeng, Ming et al. (2007) Molecular and cellular defects of skeletal muscle in an animal model of acute quadriplegic myopathy. Muscle Nerve 35:55-65

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