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Regulation of store-operated calcium channel by Mitsugumin29 in skeletal muscle aging
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Title
Regulation of store-operated calcium channel by Mitsugumin29 in skeletal muscle aging
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ETD_1478
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051074
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eng
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theses
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Topic
Physiology and Integrative Biology
Subject
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(authority = ETD-LCSH)
Topic
Calcium channels
Subject
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(authority = ETD-LCSH)
Topic
Calcium--Physiological effect
Abstract
The study of store-operated Ca2+ channel entry (SOCE) and its role in muscle contractility in young and aged skeletal muscle necessitates a thorough knowledge of the Ca2+ signaling from the sarcoplasmic reticulum (SR) that activates SOCE. Yet, all of the molecular components involved have yet to be fully elucidated, as neither T-tubule voltage sensors, nor SR ryanodine receptor Ca2+ channels, together or independently, are necessary or sufficient for the establishment of a close association between the T-tubule and SR membranes. Therefore, other protein components must be involved for the formation of triad junctional complexes.
Mitsugumin29 (MG29), a protein localized to the triad junction, may function as a structural component involved in the coupling between the SR and T-tubule, as abnormalities in both T-tubule and SR membranes have been reported in mg29(-/-) mice. In addition, muscles from these mice share many morphological and functional characteristics with muscle from aged mice, including increased susceptibility to fatigue, defective SR Ca2+ release and defective SOC function. Either of these may be responsible for the altered Ca2+ signaling in skeletal muscle during exercise and aging.
Our data suggests that SOCE is not merely important for skeletal muscle function in aging; but, it is also required for maintenance of Ca2+ signaling during repetitive stimulation under intensive muscle activity (i.e., fatigue) in the healthy state. In addition, we propose that SOCE diminishes with age, contributing to the age-associated muscle weakness. Finally, we find that while SOCE is a functional marker of muscle performance in aging, MG29 is a molecular marker, as SOCE is compromised in aged wild type mice through the decreased expression of MG29. Therefore, mg29(-/-) mice can serve as an appropriate model for the study of skeletal muscle aging. Through this project, we have begun to understand the physiological function of SOCE and MG29 and their contribution to muscle contractility in both young and aged mice.
Mitsugumin29 (MG29), a protein localized to the triad junction, may function as a structural component involved in the coupling between the SR and T-tubule, as abnormalities in both T-tubule and SR membranes have been reported in mg29(-/-) mice. In addition, muscles from these mice share many morphological and functional characteristics with muscle from aged mice, including increased susceptibility to fatigue, defective SR Ca2+ release and defective SOC function. Either of these may be responsible for the altered Ca2+ signaling in skeletal muscle during exercise and aging.
Our data suggests that SOCE is not merely important for skeletal muscle function in aging; but, it is also required for maintenance of Ca2+ signaling during repetitive stimulation under intensive muscle activity (i.e., fatigue) in the healthy state. In addition, we propose that SOCE diminishes with age, contributing to the age-associated muscle weakness. Finally, we find that while SOCE is a functional marker of muscle performance in aging, MG29 is a molecular marker, as SOCE is compromised in aged wild type mice through the decreased expression of MG29. Therefore, mg29(-/-) mice can serve as an appropriate model for the study of skeletal muscle aging. Through this project, we have begun to understand the physiological function of SOCE and MG29 and their contribution to muscle contractility in both young and aged mice.
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electronic resource
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xi, 92 p. : ill.
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Ph.D.
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Includes bibliographical references (p. 71-87)
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by Angela M. Thornton
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Thornton
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Angela M.
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Angela M. Thornton
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Merrill
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Gary
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chair
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Gary Merrill
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Ma
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Jianjie
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Jianjie Ma
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Craelius
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William
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William Craelius
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Brotto
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Marco
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Marco Brotto
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Rutgers University
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Graduate School - New Brunswick
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2009
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2009-01
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Rutgers University Electronic Theses and Dissertations
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Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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doi:10.7282/T38G8KXK
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ETD doctoral
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The author owns the copyright to this work.
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Open
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Non-exclusive ETD license
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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