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Blaauw, Bert (2007) The effects of Akt overexpression in normal and dystrophic skeletal muscle. [Ph.D. thesis]

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Abstract (english)

Lengthening (eccentric) contractions are known to induce skeletal muscle damage. Skeletal muscles of the dystrophin-deficient mdx mouse are especially sensitive to damage caused by lengthening contractions. Mild protocols of lengthening contractions, that cause no force decrement in normal mouse muscles, were found to cause a marked reduction in the maximal force produced by mdx muscles. The altered response of mdx muscles is considered to be due to sarcolemmal fragility, since no difference in force deficit after lengthening contractions was detected between mdx and control skinned fibers. We have developed an in vivo model to quantify the susceptibility of mdx mice muscles to eccentric contractions and showed a marked force decrease in the gastrocnemius of these animals.
We generated a transgenic mouse in which an inducible constitutively active form of Akt1 can be expressed selectively in adult skeletal muscle. We found that activation of Akt is sufficient to induce rapid and functional skeletal muscle hypertrophy. We crossed mdx mice with Akt transgenic mice and show a clear protection against damage from lengthening contractions after 3 weeks of Akt activation. Surprisingly, this protection is not correlated to muscle hypertrophy and is independent on the mTOR-pathway since rapamycin-treatment doesn’t inhibit the protective effect of Akt.
Protection against damage occurs on the mofibrillar level, most likely mitigated by an increase of utrophin leading to a reinforced cytoskeleton.

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EPrint type:Ph.D. thesis
Tutor:Schiaffino, Stefano
Supervisor:Reggiani, Carlo
Ph.D. course:Ciclo 20 > Scuole per il 20simo ciclo > BIOSCIENZE > NEUROBIOLOGIA
Data di deposito della tesi:17 December 2007
Anno di Pubblicazione:17 December 2007
More information:Bella tesi
Key Words:dystrophy, akt, skeletal muscle, eccentric contractions, hypertrophy
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/09 Fisiologia
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Scienze Biomediche Sperimentali
Codice ID:612
Depositato il:11 Nov 2008
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