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A Study on the Physiological Role of Skeletal Muscle Rho Kinase 2
Başlık:
A Study on the Physiological Role of Skeletal Muscle Rho Kinase 2
Yazar:
Chen, Anna, author.
ISBN:
9780438084285
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (148 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: James K. Liao Committee members: Matthew Brady; Ronald Cohen; Elizabeth McNally.
Özet:
The aim of this dissertation project is to study the physiological role of Rho-associated coiled-coil kinase (ROCK) 2 in skeletal muscle. ROCK is a ubiquitous serine/threonine kinase with clinical implications in wide range of pathologies including hypertension, metabolic syndrome and Parkinson's Disease. Previous studies have attempted to investigate ROCK's physiological role, but outstanding conflicts exists due to absence of isoform-specific and tissue-specific tools. To study ROCK2's role in the skeletal muscle, the Liao lab has generated a novel genetic mouse model with a skeletal muscle-specific deletion of ROCK2 (hereby known as MYO R2KO). MYO R2KO demonstrate a decrease in endurance phenotype with no change in muscular strength. We linked the lower endurance with a lower proportion of oxidative fibers in MYO R2KO mice. Additional, ROCK2 deficient mice have an obese phenotype on a 43% high fat diet (HFD). Consequently, we measured skeletal muscle substrate utilization. There was no difference in glycolysis, but ROCK2 deficient muscles exhibited lower fatty acid oxidation. Next, we determined in vitro that the decrease in fatty acid oxidation is associated with mitochondrial dysfunction. Cellular and molecular studies demonstrated that mitochondrial dysfunction is caused by decreased mitochondrial fission potentially ROCK regulation of F-Actin formation. In conclusion, skeletal muscle ROCK2 regulates endurance performance through its impact on mitochondrial function. These findings suggest that skeletal muscle ROCK2 may be a viable target to treat mitochondria dysfunction with long term implications for multiple diseases including Type 2 Diabetes Mellitus and skeletal muscle atrophy.
Notlar:
School code: 0330
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(691033.1) | 691033-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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