Mechanical Stretch and Electrical Stimulation in Mouse Skeletal Muscle in Vivo: Initiation of Hypertrophic Signaling

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Please use this identifier to cite or link to this item: http://hdl.handle.net/1853/5074

Title: Mechanical Stretch and Electrical Stimulation in Mouse Skeletal Muscle in Vivo: Initiation of Hypertrophic Signaling
Author: Brathwaite, Ricky Christopher
Abstract: Skeletal muscle has an integral role in many activities. Although mechanical stretch and active force generation are known to be required for the maintenance of healthy muscle function, the mechanism by which those signals mediate muscle growth is unknown. This project was based on the hypothesis that stretch and force generation activate the Calcineurin/NFAT pathway and induce Cox-2 expression and initiate muscle hypertrophy. The specific aims of this study were to 1) develop a minimally invasive system capable of initiating hypertrophic signaling in mice, 2) characterize the effects of isometric activation, passive lengthening, and active lengthening on signaling cascades, and 3) determine the involvement of the Calcineurin/NFAT pathway and activation of COX-2 gene expression. We propose a pathway in which stimuli increase intracellular calcium, which activates the phosphatase calcineurin. Calcineurin dephosphorylates NFAT, which is translocated into the nucleus and initiates transcription of the COX-2 gene. COX-2 mediated synthesis of PGG2 is the rate-limiting step in bioactive prostaglandin synthesis. Prostaglandins then stimulate known hypertrophic signals including the PI-3 Kinase and MAP Kinase signaling cascades.
Type: Thesis
URI: http://hdl.handle.net/1853/5074
Date: 2004-07-12
Publisher: Georgia Institute of Technology
Subject: PI3 Kinase
MAP Kinases
NFAT
Skeletal muscle
COX-2
Exercise
Stimulation
Stretch
Mouse
Department: Bioengineering
Advisor: Committee Chair: Thomas Burkholder; Committee Member: Cheng Zhu; Committee Member: Grace Pavlath
Degree: M.S.

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