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https://hdl.handle.net/2142/84946
Description
Title
Roles of Zinc in Skeletal Muscle Cells Growth
Author(s)
Zhang, Xiangfeng
Issue Date
2006
Doctoral Committee Chair(s)
Novakofski, Jan
Department of Study
Nutritional Sciences
Discipline
Nutritional Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Physiology
Language
eng
Abstract
Zinc deficiency impairs skeletal muscle growth in both humans and animals independently of decreased food intake. Insulin-like growth factor (IGF) is the primary regulator of postnatal muscle growth and there is substantial evidence that the effects of zinc deficiency alter IGF mediated muscle growth. The overall goal of this thesis was to examine how zinc altered IGF effects on muscle growth. To determine which components might interact with zinc, an assay was developed to determine the affinity of proteins in the IGF system for zinc based on competition between a protein and the fluorescent zinc indicator, FluoZin-3. This assay yielded affinities as follows IGF-1R > IGFBP-5 > IGF-2R > IGFBP-4 > IGFBP-2 ≈ IGFBP-3. The estimated Kd for zinc ranged from 27 nM to 340 nM. To test the hypothesis that zinc enhanced IGF activity through altering IGFBP binding to IGF, the effects of zinc on IGFBP-3 inhibition of myoblast proliferation was examined. Zinc at concentrations that altered cell proliferation did not alter IGFBP-3 inhibition of IGF activity. The effects of extracellular zinc on IGF-1R signal transduction were examined using the non-membrane permeable chelator DTPA. Zinc was important for IGF activity via both IGF-1R and the insulin receptor. The major signal transduction pathway for IGF-I stimulated myoblast proliferation was also examined. However, phosphorylated MAPK and total cyclin D1 were independent of zinc depletion. Further experiments demonstrated that zinc depletion increased expression of the p21cip cell cycle. This previously unreported effect of zinc depletion on a cell cycle inhibitor could help explain decreased myoblast proliferation in zinc deficiency.
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