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Multi-Tissue Examination Of Exercise Or Metformin On The Consequences Of Doxorubicin Treatment, Amy Dee Mackay
Multi-Tissue Examination Of Exercise Or Metformin On The Consequences Of Doxorubicin Treatment, Amy Dee Mackay
Theses and Dissertations
Doxorubicin (DOX) is an effective chemotherapeutic treatment with lasting deleterious side effects in heart and skeletal muscle. As an increased percentage of patients live many years past their cancer treatments, addressing the long-term side effects of chemotherapy treatment becomes critical. In an attempt to prevent heart and skeletal muscle damage caused by DOX, two co-treatments, exercise (EX) or metformin (MET) were studied for their effectiveness in maintaining muscle function, mitochondrial respiration and iron regulation. DOX is known to bind with iron, contributing to oxidative damage resulting in cardiac and skeletal muscle toxicity. However, the degree to which the toxic side …
Lkb1 Regulation Of High-Fat Diet-Induced Adaptation In Mouse Skeletal Muscle, Ting Chen
Lkb1 Regulation Of High-Fat Diet-Induced Adaptation In Mouse Skeletal Muscle, Ting Chen
Theses and Dissertations
Ad libitum high-fat diet (HFD)-induced obesity leads to insulin resistance in skeletal muscle, altered gene expression, and altered growth signaling, all of which contributes to pathological changes in metabolism. Liver kinase B1 (LKB1) is an important metabolism regulator. The purpose of this dissertation was to understand how knocking out LKB1 influences HFD induced adaptations in mouse skeletal muscle. To do so, control and skeletal muscle LKB1 knock-out (LKB1-KO) mice were put on either standard diet (STD) or HFD for 1 week or 14 weeks, or put on the HFD for 14 weeks and then switched to STD for 1 week …
The Effects Of Aging On Skeletal Muscle Ampk Activation And An Analysis Of Chronic Aicar Treatment On The Aging Phenotype, Shalene E. Hardman
The Effects Of Aging On Skeletal Muscle Ampk Activation And An Analysis Of Chronic Aicar Treatment On The Aging Phenotype, Shalene E. Hardman
Theses and Dissertations
AMP-activated protein kinase (AMPK), a metabolic regulator, acts in opposition to many of the effects of aging and may provide insights into the development of sarcopenia. However, the effect of aging on AMPK activation is unclear. The purpose of this dissertation was to: 1) clarify the controversy concerning the activation of AMPK in response to endurance-like exercise in aged skeletal muscle; 2) address mechanisms for the age-associated alterations in AMPK activation; and 3) address the known benefits of chronic AICAR treatment in aged skeletal muscle. First, to clarify the effect of age on AMPK activation, young adult (YA) (8 mo.) …
Iron Deficiency Causes A Shift In Amp-Activated Protein Kinase (Ampk) Catalytic Subunit Composition In Rat Skeletal Muscle, John Merrill
Iron Deficiency Causes A Shift In Amp-Activated Protein Kinase (Ampk) Catalytic Subunit Composition In Rat Skeletal Muscle, John Merrill
Theses and Dissertations
To determine effects of iron deficiency on AMPK activation and signaling, as well as the AMPKα subunit composition in skeletal muscle, rats were fed a control (C=50-58 mg/kg Fe) or iron deficient (ID=2-6 mg/kg Fe) diet for 6-8 wks. Their respective hematocrits were 47.5% ± 1.0 and 16.5% ± 0.6. Iron deficiency resulted in 28.3% greater muscle fatigue (p<0.01) in response to 10 min of stimulation (1 twitch/sec) and was associated with a greater reduction in phosphocreatine (C: Resting 24.1 ± 0.9 micromol/g, Stim 13.1 ± 1.5 micromol/g; ID: Resting 22.7 ± 1.0 micromol/g, Stim 3.2 ± 0.7 micromol/g; p<0.01) and ATP levels (C: Resting 5.89 ± 0.48 micromol/g, Stim 6.03 ± 0.35 micromol/g; ID: Resting 5.51 ± 0.20 micromol/g, Stim 4.19 ± 0.47 micromol/g; p<0.05). AMPK activation increased with stimulation in muscles of C and ID animals. A reduction in Cytochrome c and other iron-dependent mitochondrial proteins was observed in ID animals (p<0.01). The AMPK catalytic subunit (alpha) was also examined because both isoforms are known to play different roles in responding to energy challenges. In ID animals, AMPK alpha2 subunit protein content was reduced to 71.6% of C (p<0.05), however this did not result in a significant difference in resting AMPK alpha2 activity. AMPK alpha1 protein was unchanged, however an overall increase in AMPK alpha1 activity was observed (C: 0.91 pmol/mg/min; ID: 1.63 pmol/mg/min; p<0.05). Resting phospho Acetyl CoA Carboxylase (pACC) was unchanged. This study indicates that chronic iron deficiency causes a shift in the expression of AMPK alpha subunit composition and potentially altered sensitivity to cellular energy challenges.
Spatial Distribution And Modulation Of Nitric Oxide Synthase In A Hypertensive Rat Model, Andrew Yannaccone
Spatial Distribution And Modulation Of Nitric Oxide Synthase In A Hypertensive Rat Model, Andrew Yannaccone
Theses and Dissertations
There are gaps in the fundamental understanding of the expression of nitric oxide synthases (NOS) in the microvasculature. We examined co-localization of NOS1 (nNOS), NOS2 (iNOS) and NOS3 (eNOS) in the spinotrapezius muscle of young adult male Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats according to fiber type using immunohistochemistry and brightfield microscopy. Data regarding fiber distribution, population and morphology data were collected. Alkaline phosphatase staining was used to determine capillary density and average number of capillaries around a fiber. Gel electrophoresis and Western blot techniques were used to compare myosin heavy chain (MHC) protein expression with fiber type population …
Liver Kinase B1/Amp-Activated Protein Kinase Signaling In The Diaphragm, Jacob D. Brown
Liver Kinase B1/Amp-Activated Protein Kinase Signaling In The Diaphragm, Jacob D. Brown
Theses and Dissertations
The Liver Kinase B1 (LKB1)/AMP-Activated Protein Kinase (AMPK) signaling pathway is a major regulator of skeletal muscle metabolic processes. During exercise, LKB1-mediated phosphorylation of AMPK leads to its activation, promoting mitochondrial biogenesis and glucose transport, among other effects. The roles of LKB1 and AMPK have not been fully characterized in the diaphragm. Two methods of AMPK activation were used to characterize LKB1/AMPK signaling in diaphragms from muscle-specific LKB1 knockout (KO) and littermate control (C) mice: (1) acute injection of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and (2) 5-min direct electrical stimulation (ES) of the diaphragm. Diaphragms were excised 60 minutes post-AICAR injection and …