Medicine and Health Sciences Commons^™

The Effects Of Creatine Supplementation On Muscle Synthesis And Fitness Levels In Drosophila Melanogaster Using A Model Of Muscle Atrophy, Kevin Williams

Honors Program Projects

This study examines whether an inhibited electron transport chain can be aided with supplemented creatine to make up for the challenged adenosine triphosphate (ATP) production mechanism. The electron transport chain is a series of protein complexes in the mitochondrial membrane that transfer electrons and couples this reaction with the transfer of protons across the membrane to produce ATP. The differences between male and female flies and the supplementation of creatine at a 0.15% concentration was studied. The relationship between these components was studied over the course of two 3-week trials using a fly treadmill and Drosophila. The effects of creatine …

The Effects Of Creatine Supplementation On Muscle Synthesis And Fitness Levels In Drosophila Melanogaster Using A Model Of Muscle Atrophy, Kevin Williams

Scholar Week 2016 - present

This study examines whether an inhibited electron transport chain can be aided with supplemented creatine to make up for the challenged adenosine triphosphate (ATP) production mechanism. The differences between male and female flies and the supplementation of creatine at a 0.15% concentration was studied. The relationship between these components was studied over the course of two 3-week trials using a fly treadmill and Drosophila. The effects of creatine on a mitochondrial disease modeled Drosophila melanogaster were analyzed by tracking climbing speed, leg width, and body width. The research yielded largely minimal differences between supplemented and non-supplemented, mutated, and non-mutated …

Real-Time Visualization Of Cytosolic And Mitochondrial Atp Dynamics In Response To Metabolic Stress In Cultured Cells, Donnell White Iii, Lothar Lauterboeck, Parnia Mobasheran, Tetsuya Kitaguchi, Antoine H. Chaanine, Qinglin Yang

School of Medicine Faculty Publications

Adenosine 50 triphosphate (ATP) is the energy currency of life, which is produced in mitochondria (~90%) and cytosol (less than 10%). Real-time effects of metabolic changes on cellular ATP dynamics remain indeterminate. Here we report the design and validation of a genetically encoded fluorescent ATP indicator that allows for real-time, simultaneous visualization of cytosolic and mitochondrial ATP in cultured cells. This dual-ATP indicator, called smacATPi (simultaneous mitochondrial and cytosolic ATP indicator), combines previously described individual cytosolic and mitochondrial ATP indicators. The use of smacATPi can help answer biological questions regarding ATP contents and dynamics in living cells. As expected, 2-deoxyglucose …

Environmental Cleaning Evaluation Project For Rural Tribal Health Center, Brad Strait

Capstone Experience

This Tribal health clinic is located on reservation land and serves a community of approximately 1,550 members located over 64,000 acres located in Nevada and California. The clinic offers general health practice and podiatry at its central clinic with satellite offices located off-reservation offering dentistry, optometry, and behavioral health. The clinic is operated by Tribal staff and partners with the Indian Health Service (IHS) for environmental survey on an annual basis for compliance with Accreditation Association for Ambulatory Health Care (AAAHC) standards. While this clinic only offers outpatient services, the disinfection and cleaning protocols are an important step in limiting …

Genetically Encoded Atp Biosensors For Direct Monitoring Of Cellular Atp Dynamics, Donnell White, Qinglin Yang

School of Medicine Faculty Publications

Adenosine 5′-triphosphate, or ATP, is the primary molecule for storing and transferring energy in cells. ATP is mainly produced via oxidative phosphorylation in mitochondria, and to a lesser extent, via glycolysis in the cytosol. In general, cytosolic glycolysis is the primary ATP producer in proliferative cells or cells subjected to hypoxia. On the other hand, mitochondria produce over 90% of cellular ATP in differentiated cells under normoxic conditions. Under pathological conditions, ATP demand rises to meet the needs of biosynthesis for cellular repair, signaling transduction for stress responses, and biochemical processes. These changes affect how mitochondria and cytosolic glycolysis function …

Structural And Functional Features Of The P2x4 Receptor: An Immunological Perspective, Jean M. Kanellopoulos, Cássio Luiz Coutinho Almeida-Da-Silva, Sirje Rüütel Boudinot, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Extracellular nucleotides are important mediators of activation, triggering various responses through plasma membrane P2 and P1 receptors. P2 receptors are further subdivided into ionotropic P2X receptors and G protein-coupled P2Y receptors. P2X4 is an ATP-gated cation channel broadly expressed in most tissues of the body. Within the P2X family, P2X4 has a unique subcellular distribution, being preferentially localized in lysosomes. In these organelles, high ATP concentrations do not trigger P2X4 because of the low pH. However, when the pH increases to 7.4, P2X4 can be stimulated by intra-lysosomal ATP, which is in its active, tetra-anionic form. Elucidation of P2X4, P2X3 …

Effect Of Energy Metabolism On Nf-Kb Activity In Ovarian Cancer, Simren K. Bagri

Undergraduate Research Posters

NF-kB is a transcription factor involved in cancer cell growth and survival. The activation of NF-kB can be assessed by monitoring phosphorylation of RelA p65 at Ser-536, which is a surrogate of the NF-kB transcription factor activation. The objective of this study was to determine if the loss of ATP leads to NF-kB deficiency and thus, apoptotic cell death of “bad” cells in ovarian cancer cells. The independent variables were metformin (Met), an anti-diabetic medicine, another compound MinB functionally similar to Met and a glucose transporter inhibitor BAY-876. The dependent variables were the resulting effect of Met and MinB on …

Cholesterol Regulation Of Pulmonary Endothelial Calcium Entry Following Chronic Hypoxia, Bojun Zhang

Biomedical Sciences ETDs

Chronic hypoxia (CH)-induced pulmonary hypertension (PH) is associated with diminished ATP-induced endothelial Ca2+ entry as well as membrane cholesterol in pulmonary arteries. Store-operated Ca2+ entry (SOCE) and depolarization-induced Ca2+ entry are major components of the response to ATP and are similarly decreased after CH. Because endothelium-dependent vasodilation is closely associated with pulmonary endothelial [Ca2+]i, the blunted agonist-induced Ca2+ influx in pulmonary artery endothelial cells (PAEC) may contribute to the development of CH-induced PH. Interestingly, impaired agonist-induced Ca2+ influx in PAEC following CH can be restored by membrane cholesterol supplementation. In the current studies, we hypothesized that impaired Ca2+ entry in …

P2x2 Dominant Deafness Mutations Have No Negative Effect On Wild-Type Isoform: Implications For Functional Rescue And In Deafness Mechanism, Yan Zhu, Juline Beudez, Ning Yu, Thomas Grutter, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

The P2X2 receptor is an ATP-gated ion channel, assembled by three subunits. Recently, it has been found that heterozygous mutations of P2X2 V60L and G353R can cause autosomal dominant nonsyndromic hearing loss. However, the underlying mechanism remains unclear. The fact that heterozygous mutations cause deafness suggests that the mutations may have dominant-negative effect (DNE) on wild-type (WT) P2X2 isoforms and/or other partners leading to hearing loss. In this study, the effect of these dominant deafness P2X2 mutations on WT P2X2 was investigated. We found that sole transfection of both V60L and G353R deafness mutants could efficiently target to the plasma …

Tp53-Inducible Glycolysis And Apoptosis Regulator (Tigar) Metabolically Reprograms Carcinoma And Stromal Cells In Breast Cancer., Ying-Hui Ko, Marina Domingo-Vidal, Megan Roche, Zhao Lin, Diana Whitaker-Menezes, Erin Seifert, Claudia Capparelli, Madalina Tuluc, Ruth C. Birbe, Patrick Tassone, Joseph M. Curry, Àurea Navarro-Sabaté, Anna Manzano, Ramon Bartrons, Jaime Caro, Ubaldo E. Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

A subgroup of breast cancers has several metabolic compartments. The mechanisms by which metabolic compartmentalization develop in tumors are poorly characterized. TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. Hence we set out to determine the effects of TIGAR expression on breast carcinoma and fibroblast glycolytic phenotype and tumor growth. The overexpression of this bisphosphatase in carcinoma cells induces expression of enzymes and transporters involved in the catabolism of lactate and glutamine. Carcinoma cells overexpressing TIGAR have higher oxygen consumption rates …

Microbial Activity And Airborne Culturable Microbial Concentrations In South Georgia Homes, Alli Mcinerney, Jacquelyn Lewis, Errol Spence, Bushra Shah, Atin Adhikari

GS4 Georgia Southern Student Scholars Symposium

Indoor microorganisms and microbial allergens can lead to harmful respiratory effects in the human body such as allergies, asthma, chronic bronchitis, infections, and even contamination of food stuffs. This study was conducted in order to test the indoor microbial pollutants in local Statesboro homes, and relate the findings to respiratory disease symptoms of occupants. Thus far, samples have been collected and data analyzed for 15 homes. This specific part of the study focuses on the amount of adenosine triphosphate (ATP) in homes. ATP is a source of energy produced through glucose metabolism and the citric acid cycle. ATP levels can …

Metabolic Danger Signals, Uric Acid And Atp, Mediate Inflammatory Cross-Talk Between Hepatocytes And Immune Cells In Alcoholic Liver Disease., Jan Petrasek, Arvin Iracheta-Vellve, Banishree Saha, Abhishek Satishchandran, Karen Kodys, Katherine Fitzgerald, Evelyn Kurt-Jones, Gyongyi Szabo

Gyongyi Szabo

Inflammation defines the progression of ALD from reversible to advanced stages. Translocation of bacterial LPS to the liver from the gut is necessary for alcohol-induced liver inflammation. However, it is not known whether endogenous, metabolic danger signals are required for inflammation in ALD. Uric acid and ATP, 2 major proinflammatory danger signals, were evaluated in the serum of human volunteers exposed to a single dose of ethanol or in supernatants of primary human hepatocytes exposed to ethanol. In vitro studies were used to evaluate the role of uric acid and ATP in inflammatory cross-talk between hepatocytes and immune cells. The …

Novel Techniques For Investigating The Regulation Of Skeletal Muscle Hemodynamics, Baraa K. Al-Khazraji

Electronic Thesis and Dissertation Repository

The effect of the sympathetic nervous system (SNS) on blood flow distribution within skeletal muscle microvasculature is conditional upon regional activation of SNS receptors. Due to a lack of appropriate experimental models and techniques, no study has systematically evaluated the effect of SNS receptor activation in continuously branching skeletal muscle arteriolar trees. In line with previous work, we hypothesize that there will be a spatially-dependent distribution of sympathetic receptor activation along the arteriolar tree. Specifically, we anticipate a progressive decrease of adrenergic activation and a progressive increase of peptidergic and purinergic activation with increasing arteriolar order. We developed a novel …

Impaired Skeletal Muscle Blood Flow Control With Advancing Age In Humans: Attenuated Atp Release And Local Vasodilation During Erythrocyte Deoxygenation, Brett S. Kirby, Anne R. Crecelius, Wyatt F. Voyles, Frank A. Dinenno

Anne R. Crecelius

Rationale: Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown. Objective: To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation. Methods and Results: We showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, …

Lkb1 Deficient Non-Small Cell Lung Cancer Cells Are Vulnerable To Energy Stress Induced By Atp Depletion, Chao Yang

Dissertations & Theses (Open Access)

Lung cancer is the second most frequent cancer in United States, which represents about 13.5% of new cancer cases every year. It accounts for about 27.2% of all cancer related deaths, which is more than the sum of deaths caused by prancretic, breast and colorectal. On average, only about 16% of lung cancer patients survive beyond 5 years. LKB1 is the third most mutated gene in lung cancer. It has been shown that LKB1 is mutated in at least 15% to 30% of NSCLC. Tumor with LKB1 mutation is associated with poor differentiation, high metastasis and worse response to chemotherapy. …

Impaired Skeletal Muscle Blood Flow Control With Advancing Age In Humans: Attenuated Atp Release And Local Vasodilation During Erythrocyte Deoxygenation, Brett S. Kirby, Anne R. Crecelius, Wyatt F. Voyles, Frank A. Dinenno

Health and Sport Science Faculty Publications

Rationale: Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown.

Objective: To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation.

Methods and Results: We showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, …

Porcine Bladder Urothelial, Myofibroblast And Detrusor Muscle Cells: Characterisation And Atp Release, Ying Cheng, Kylie J. Mansfield, Shaun L. Sandow, Prajni Sadananda, Elizabeth Burcher, Kate H. Moore

Graduate School of Medicine - Papers (Archive)

ATP is released from the bladder mucosa in response to stretch, but the cell types responsible are unclear. Our aim was to isolate and characterize individual populations of urothelial, myofibroblast, and detrusor muscle cells in culture, and to examine agonist-stimulated ATP release. Using female pig bladders, urothelial cells were isolated from bladder mucosa following trypsin-digestion of the luminal surface. The underlying myofibroblast layer was dissected, minced, digested, and cultured until confluent (10–14 days). A similar protocol was used for muscle cells. Cultures were used for immunocytochemical staining and/or ATP release investigations. In urothelial cultures, immunoreactivity was present for the cytokeratin …

Translocation And Function Of Akt In The Mitochondria, Keri A. Mans

All ETDs from UAB

The ubiquitously expressed kinase Akt is a known survival protein, and is involved in multiple cell signaling cascades, notably the phosphatidylinositol 3-kinase (PI3K) pathway. Active Akt translocates from the plasma membrane to different subcellular compartments, including mitochondria, where it phosphorylates compartment-specific substrates. The mechanism of this translocation and the specific function of Akt within the mitochondria remains a mystery. The goals of this study were to elucidate the mechanism by which Akt enters the mitochondria and examine the role of Akt in mitochondrial function. Finally, the possibilities of using post-mortem human brain tissue to study mitochondrial function in normal and …

Lactate Dyscrasia: A Novel Explanation For Amyotrophic Lateral Sclerosis, Sivan Vadakkadath Meethal, Craig Atwood

Research outputs pre 2011

Amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease) is a progressive debilitating neurodegenerative disease with no cure. We propose a novel molecular model for the pathogenesis of ALS that involves an adenosine triphosphate (ATP)-dependent muscle neuronal lactate shuttle (MNLS) at the neuromuscular junction (NMJ) to regulate the flow of lactate from muscle to neurons and vice versa. Failure of the MNLS due to respiratory chain dysfunction is proposed to result in lactate toxicity and degeneration of nerve endings at the NMJ leading to nerve terminus dysjunction from the muscle cell. At a critical threshold where denervation outpaces reinnervation, a vicious cycle …

Purines And The Anti-Epileptic Actions Of Ketogenic Diets, Susan A. Masino, Masahito Kawamura Jr., David N. Ruskin, Jeremy Gawryluk, Xuesong Chen, Jonathan D. Geiger

Faculty Scholarship

Ketogenic diets are high in fat and low in carbohydrates and represent a well-established and effective treatmentalternative to anti-epileptic drugs. Ketogenic diets are used for the management of a variety of difficult-to-treat or intractableseizure disorders, especially pediatric refractory epilepsy. However, it has been shown that this dietary therapycan reduce seizures in people of all ages, and ketogenic diets are being applied to other prevalent medical conditions suchas diabetes. Although used effectively to treat epilepsy for nearly 90 years, the mechanism(s) by which ketogenic dietswork to reduce seizures remain ill-understood. One mechanism receiving increased attention is based on findings that ketogenicdiets …

Activation Of Extracellular-Signal Regulated Kinase (Erk1/2) By Fluid Shear Is Ca2+- And Atp-Dependent In Mc3t3-E1 Osteoblasts, Dawei Liu, Damian C. Genetos, Ying Shao, Derik J. Geist, Jiliang Li, Hua Zhe Ke, Charles H. Turner, Randall L. Duncan

School of Dentistry Faculty Research and Publications

To determine the role of Ca²⁺ signaling in activation of the Mitogen-Activated Protein Kinase (MAPK) pathway, we subjected MC3T3-E1 pre-osteoblastic cells to inhibitors of Ca²⁺ signaling during application of fluid shear stress (FSS). FSS only activated ERK1/2, rapidly inducing phosphorylation within 5 min of the onset of shear. Phosphorylation of ERK1/2 (pERK1/2) was significantly reduced when Ca_i²⁺ was chelated with BAPTA or when Ca²⁺ was removed from the flow media. Inhibition of both the L-type voltage-sensitive Ca²⁺ channel and the mechanosensitive cation-selective channel blocked FSS-induced pERK1/2. Inhibition of phospholipase C with U73122 significantly reduced …

Oxidative Stress And Cell Death In Osmotically Swollen Glial Cells, Crystal Elaine Stuckey

Browse all Theses and Dissertations

Regulation of normal volume is an important aspect of cell homeostasis. Possible mechanisms which signal volume regulation are increasing the rate of reactive oxygen species (ROS) production and release of ATP for interaction with purinergic receptors. We examined whether an increase in ROS production during cell swelling also led to cell injury of C6 glioma cells. Cells were loaded with 5,6-carboxy-2,7-dihydrofluorscein diacetate (DCFDA) to fluoroscopically measure the rate of cellular ROS production and were perfused with phosphate-buffered saline solutions (PBS) containing 100 μM carbenoxolone to inhibit dye efflux. Cell death was determined cytometrically and by measuring the release of lactate …

The Effect Of Simvastatin Treatment On Plasma Ubiquinone, Blood Atp Concentrations, Total Antioxidant Capacity And Muscle Related Markers, Emel Alteki̇n, Banu Önvural, Canan Çoker, Sema Güneri̇, Sezer Çalişkan

Turkish Journal of Medical Sciences

It has been hypothesized that treating hypercholesterolemic patients with statins will lead not only to a reduction in cholesterol, but also to inhibited synthesis of other compounds that derive from the synthetic pathway of cholesterol. One important by-product is ubiquinone (CQ), which has a pivotal role in mitochondrial electron transport and antioxidant activity. We therefore investigated the effect of 2 months of simvastatin treatment (20 mg/day) on blood ATP concentration, plasma total antioxidant capacity and ubiquinone levels in 17 hypercholesterolemic patients (age range: 40 to 65). To evaluate the possible muscle-related side effects, plasma CK activity and myoglobin concentrations were …

The Effect Of Experimental Gastric Dilatation-Volvulus On The Adenosine Triphosphate Content And Cellular Permeability Of The Canine Gastric And Jejunal Mucosa, Laura Elizabeth Peycke

LSU Master's Theses

This study was designed to characterize changes in the content of adenosine triphosphate (ATP) and cellular permeability of gastric and jejunal mucosa during gastric dilatation-volvulus (GDV). Our hypothesis stated that experimental GDV would result in a decrease in ATP content and cellular integrity of the gastric and intestinal mucosa that may improve after decompression and derotation of the stomach. Fifteen medium-to-large mixed-breed male dogs were randomly divided into three groups: GDV dogs, Ischemia dogs and Control dogs. All dogs were maintained on gas anesthesia for 210 minutes. The GDV dogs had a GDV for 120 minutes with a 90-minute period …