Item – Theses Canada

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OCLC number
56682650
Link(s) to full text
LAC copy
LAC copy
Author
Li, Minghua,1968-
Title
Alterations in the MAP kinase and PI 3-kinase signaling molecules in response to exercise, aging and des IGF-I administration in mice.
Degree
Ph. D. -- Simon Fraser University, 2002
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [2004]
Description
2 microfiches.
Notes
Includes bibliographical references.
Abstract
The MAP kinase and PI 3-kinase pathways are two important pathways involved in regulating a number of cellular functions by various factors, like growth factors and exercise. The exercise-mediated activation of these two pathways has been focused on the period immediately following exercise while their responses to exercise in the recovery period remains unclear. Insulin-like growth factor-I (IGF-I) activates these two pathways in various tissues and cells and the responses seem to be not the same among tissues. The IGF-I action was found to be diminished with the advancing of aging while exercise was shown to be able to attenuate the aging-related decreases in IGF-I action. The signalling mechanism behind these regulations remains uninvestigated. The purposes of this thesis were to investigate the regulation of these two pathways by prior exercise and des IGF-I, an IGF-I analogue, in mouse muscle. Female C57B1/6 mice aged 5 months were sacrificed 12 hours after a moderate intensity treadmill run and/or 20 minutes after des IGF-I injection. Exercise increased the phosphorylation of IRS-1, Akt-1, p70S6K and ERK1 and these changes were not associated with changes in plasma IGF-I, insulin and muscle IGF-I levels. In both skeletal and cardiac muscle, des IGF-I increased the phosphorylation of Akt-1 without changing the phosphorylation of ERK1/2. The des IGF-I-mediated increase in p70S6K phosphorylation was seen in skeletal but not cardiac muscle. In contrast, the des IGF-I-mediated phosphorylation of the transcription factor FKHR was only increased in cardiac muscle. In 24 months old mice, des IGF-I also increased the Akt-1 phosphorylation. The p70S6K phosphorylation was not increased by des IGF-I in aged skeletal muscle and prior exercise did not attenuate the age-related resistance to des IGF-I at the p70S6K level. The results demonstrated that the exercise-mediated activation of the MAP kinase and PI 3-kinase pathway also appears in the recovery period. Des IGF-I had differential effects on the activation of the MAP kinase and PI 3-kinase pathways in mouse skeletal muscle and cardiac muscle. The aged skeletal muscle had a resistance at p70S6K level in response to des IGF-I while prior exercise was not able to attenuate this resistance.
ISBN
0612815951
9780612815957