Initial events in the muscle atrophy program

2006 2006

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Abstract (summary)

The aim of this dissertation was to explore alterations in human skeletal muscle during a controlled period of immobilization and following spinal cord injury (SCI). Study I examined the effects of an imposed period of immobilization of the adductor pollicis (AP) muscle on muscle function and volume in young (18-25 years) and aged (60-75 years) men. Muscle strength and volume of the AP was assessed before and after immobilization. Results from Study I show that although the older and younger adults had disparate losses in muscle volume they experienced similar losses in muscle strength. These results confirm that even short periods of inactivity promote more rapid losses in muscle volume in older adults, while the ability to generate force is maintained.

Study II and Study III of this dissertation explored the molecular alterations in human skeletal muscle in response to immobilization or SCI. Muscle biopsies were analyzed at both the transcriptional (microarray analysis, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR)) and translational (Western blotting, Immunohistochemistry (IHC)) level. In Study II, the knee joint of five young men (aged 18-25 years) was immobilized, and muscle biopsies were performed before and after 48h of leg immobilization. Immobilization resulted in increased expression of genes involved in the ubiquitin proteasome pathway and metallothionein function, but no change in respective protein products. However, results of Study II also showed a decrease in gene expression and protein products for the collagens, which are involved in extracellular matrix (ECM) integrity, indicating that disruption to the ECM is an initial step in the muscle atrophy program following immobilization.

In Study III, analysis of muscle biopsies taken two and five days post-SCI, compared to healthy controls, showed increased gene expression for genes that encode components of the ubiquitin proteasome pathway, metallothioneins, and secretory leukocyte protease inhibitors. Western blotting and IHC showed that protein products for components of the proteolytic core and the metallothioneins increased by five days post-SCI, and protein products were localized to the ECM. These results indicate that components of the ECM are initial targets of proteolytic activity within the first days following SCI.

Indexing (details)

Anatomy & physiology;
0433: Anatomy & physiology
0433: Animals
0410: Microbiology
0382: Rehabilitation
0382: Therapy
Identifier / keyword
Health and environmental sciences; Biological sciences; Adductor pollicis; Muscle atrophy; Spinal cord injury
Initial events in the muscle atrophy program
Urso, Maria L.
Number of pages
Publication year
Degree date
School code
DAI-B 67/04, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
9780542656712, 054265671X
Clarkson, Priscilla M.
University of Massachusetts Amherst
University location
United States -- Massachusetts
Source type
Dissertations & Theses
Document type
Dissertation/thesis number
ProQuest document ID
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
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