Key result
Mechanical overload in transgenic mice induces a ~4-fold increase in CAT activity despite regulatory mutations.
Beta-MHC transgenes are induced by mechanical overload via mechanisms that do not exclusively require the MCAT, C-rich, or beta e3 subregions.
Answers are grounded in this paper and cite their sources.
No immediate clinical implications for hypertrophy; leaves open alternative regulatory elements for beta-MHC induction in overload models.
Mechanical overload leads to hypertrophy, increased type I fiber composition, and beta-myosin heavy chain (beta-MHC) induction in the fast-twitch plantaris muscle. To better understand the mechanism(s) involved in beta-MHC induction, we have examined inducible expression of transgenes carrying the simultaneous mutation of three DNA regulatory subregions [muscle CAT (MCAT), C-rich, and beta e3] in the context of either 5,600-base pair (bp; beta 5.6mut3) or 600-bp (beta 0.6mut3) beta-MHC promoter in overloaded plantaris muscles of transgenic mice. Protein extract from mechanically overloaded plantaris muscle of mice, harboring either mutant transgene beta 5.6mut3 or beta 0.6mut3, showed an unexpected 2.8- to 4.5-fold increase in chloramphenicol acetyltransferase (CAT) specific activity relative to their respective controls. Similar results were obtained with wild-type (wt) beta-MHC transgenes (beta 5.6wt, beta 0.6wt). Histochemical staining for both myofibrillar ATPase and CAT activity and CAT immunohistochemistry revealed a striking increase in type I fibers and that CAT expression was restricted to these fibers in overloaded plantaris muscle of beta 5.6mut3 transgenic mice. Our transgenic data suggest that beta-MHC transgenes, and perhaps the endogenous beta-MHC gene, are induced by mechanical overload via a mechanism(s) that does not exclusively require the MCAT, C-rich, or beta e3 subregions.
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Tsika et al. (1996) studied Mechanical overload of skeletal muscle. Mechanical overload vs. Respective controls (non-overloaded) was evaluated on Chloramphenicol acetyltransferase (CAT) specific activity (2.8- to 4.5-fold increase). Mechanical overload of the plantaris muscle in transgenic mice induced a 2.8- to 4.5-fold increase in CAT specific activity despite simultaneous mutation of three DNA regulatory subregions.
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