Date of Award
1986
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Abstract
In order to establish a basis for studies of the development of the polymyopathy of the UM-X7.1 hamster strain, primary tongue myoblast and skin fibroblast cultures were prepared and characterized in terms of established criteria for growth and differentiation. Clonal analysis of myoblast cultures indicated that 80% of colonies judged to be fusion-competent had differentiated. Dystrophic myoblasts displayed a significantly higher plating efficiency, a longer doubling time, and a lower day-7 creatine kinase activity as compared to normal, whereas dystrophic fibroblasts exhibited significant decreases in day-2 creatine kinase and day-7 myokinase activities.;An assessment of ornithine (ODC) and S-adenosylmethionine (SAMDC) decarboxylase activities in normal and dystrophic hamster whole tissues and primary cultures revealed that these enzyme activities consistently reflect the degree of cell proliferation. The increase in dystrophic myoblast doubling time observed earlier was verified by a significantly decreased ODC activity in dystrophic myoblast extracts at 1 day in culture. No other significant differences were observed.;As part of a study on the implication of elevated Ca('2+) levels in the myofibrillar degeneration seen in dystrophic muscle, Ca('2+)-activated neutral protease (CANP) activity was measured in normal and dystrophic hamster skeletal muscle, heart and tongue tissues at the terminal stages of the disease. Since only marginal increases in dystrophic CANP activity were observed, it was concluded that an abnormal elevation in CANP levels is not directly responsible for the degeneration of these tissues at this stage in the disease.;An examination of calmodulin (CAM) levels in dystrophic hamster whole muscle and primary culture extracts revealed that an age-dependent decline in total CAM levels occurs in normal and dystrophic muscle between 2 and 12 weeks of age. Dystrophic values, however, tended to remain somewhat higher than normal, especially in 12-week-old skeletal muscle extracts. These differences were not evident at the terminal stages of the disease. No significant alterations in CAM levels were observed in dystrophic cultures despite evidence of a Ca('2+)-related abnormality in the proliferative capacity of these cells. It was concluded that CAM levels are not altered in response to the elevated intracellular Ca('2+) levels in dystrophic tissues, resulting a severe imbalance in Ca('2+)-CAM-mediated processes.
Recommended Citation
Klamut, Henry Joseph, "Biochemical Studies Related To The Progression Of Muscular Dystrophy In The Um-x71 Syrian Hamster" (1986). Digitized Theses. 1550.
https://ir.lib.uwo.ca/digitizedtheses/1550