Life Sciences Commons^™

Examination Of Anabolic Signaling And Muscle Growth With Caffeine Treatment In Overloaded Hindlimb Muscle And Electrically Stimulated Muscle Lacking Liver Kinase B1, Timothy Michael Moore

Theses and Dissertations

Skeletal muscle has the ability to increase in size (hypertrophy) after resistance is placed upon it. This hypertrophy is marked by significant upregulation of the mammalian target of rapamycin (mTOR) and its downstream targets. The upstream kinases, protein kinase B (also known as Akt) and AMP-activated protein kinase (AMPK), are two of the many regulators of the mTOR pathway. Recent studies suggest that the widely consumed neuroactive compound caffeine could potentially inhibit mTOR by acting through Akt and/or AMPK. The purpose of this thesis was to: 1) determine if caffeine can inhibit the mTOR pathway and ultimately attenuate skeletal muscle …

Haploinsufficiency Of Cardiac Myosin Binding Protein-C In The Development Of Hypertrophic Cardiomyopathy, David Barefield

Dissertations

Heart Failure is one of the leading causes of morbidity and mortality in the human population and represents a common endpoint for several diseases including inherited cardiomyopathies. Hypertrophic Cardiomyopathy (HCM) is characterized by left ventricular wall thickening, diastolic dysfunction, and sarcomere disarray. Mutations in sarcomeric protein encoding genes have been established as causative for HCM.

The gene MYBPC3, encoding cardiac myosin binding protein-C (cMyBP-C), is the second most commonly mutated gene in HCM cases. As a majority of these mutations have been determined to result in a null allele which does not produce any protein, it is thought that haploinsufficiency …

Junctional Sarcoplasmic Reticulum Protein Processing And Trafficking In Cardiac Tissue And Primary Cultured Cardiomyocytes, Naama Sleiman

Wayne State University Dissertations

Junctional SR is an important and unique ER subdomain in the adult myocyte that releases Ca2+ through the actions of an exclusive set of resident proteins. Cardiac calsequestrin (CSQ2) undergoes two co-translational modifications: N-linked glycosylation on 316Asn, and phosphorylation by protein kinase CK2 on a cluster of 3 serines in its tail. In the heart, CSQ2 molecules undergo extensive mannose trimming by ER mannosidase(s), a posttranslational process that often regulates protein breakdown. To investigate CSQ2 protein processing in cardiomyopathy models, studies were performed to test whether CSQ2 glycan structures would be altered in heart tissue from mongrel dogs induced into …