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Articles 1 - 30 of 43
Full-Text Articles in Physiology
Does Vdac2 Have A Bh3 Domain?, Lillian Ferkany
Does Vdac2 Have A Bh3 Domain?, Lillian Ferkany
Honors Theses
Mitochondrial outer membrane permeabilization (MOMP) by Bax oligomerization triggers apoptosis. BCl-2 family proteins, classified as BH3 only proteins, pro-survival proteins, or pro-apoptotic proteins, control apoptosis partly through their agonist or antagonistic effects on Bax, which are mediated by their conserved BH3 domains. All BH3 domains form an alpha helix containing 5-7 conserved hydrophobic residues, designated H0-H5, and one conserved aspartic acid that drive interaction with Bax and other ‘multi-domain’ BCl-2 members. BH3 agonists induce Bax oligomerization, while BH3 antagonists sequester Bax to prevent MOMP. We discovered that voltage dependent anion channels (VDACs) in the MOM contain a putative BH3-like domain …
Role Of Bmi1 In Acute Lung Injury, María Helena Hernández-Cuervo
Role Of Bmi1 In Acute Lung Injury, María Helena Hernández-Cuervo
USF Tampa Graduate Theses and Dissertations
Acute Lung Injury (ALI) is a set of signs and symptoms that lead to acute hypoxemic respiratory failure characterized by bilateral pulmonary infiltrates not attributed to cardiogenic origin. It is caused by a massive innate immune response, with the migration of white blood cells (neutrophils and macrophages principally) and a cytokine storm, followed by alterations in mitochondrial function, increase in reactive oxygen species production, and oxidative stress that in turn induces more mitochondrial damage. Several studies have shown that mitochondrial alterations are key events in the mechanism of ALI and reducing mitochondrial dysfunction could be a possible target in the …
Mechanisms Of Diapause And Cold Tolerance In The Colorado Potato Beetle, Jacqueline E. Lebenzon
Mechanisms Of Diapause And Cold Tolerance In The Colorado Potato Beetle, Jacqueline E. Lebenzon
Electronic Thesis and Dissertation Repository
Many temperate insects enter diapause (a state of dormancy) and enhance their cold tolerance to survive the winter. During diapause, the Colorado potato beetle (CPB, Leptinotarsa decemlineata, Coleoptera: Chrysomelidae) stops developing, lowers its metabolism, and changes its physiology to avoid freezing. The extent to which diapause confers cold tolerance in CPB is currently unknown. In my thesis, I used CPB to improve our understanding of the mechanisms underlying metabolic suppression during diapause and cellular protection at sub-zero temperatures in insects. First, I used RNA-sequencing (RNA-seq) to compare gene expression in two metabolically important tissues (the fat body and flight muscle) …
Characterizing The Effects Of Pyrroloquinoline Quinone (Pqq) Supplementation On Skeletal Muscle Mitochondrial Function And Myogenesis During Oxidative Stress And Iugr., Allyson J. Wood
Electronic Thesis and Dissertation Repository
Intrauterine growth restriction (IUGR) affects 10-15% of births and is associated with placental insufficiency (PI), resulting in fetal oxidative stress (OS). This OS is a factor in the predisposition to postnatal noncommunicable disease (NCD) of which muscle mitochondrial dysfunctional is a key aspect. Pyrroloquinoline quinone (PQQ), an antioxidant-like compound, is capable of OS reduction and promotes mitochondrial function, though limited research has focused on its effects in in utero skeletal muscle. This study sought to investigate the impact of in vitro H2O2, a model of OS, and an in vivo model of OS associated IUGR, with …
Mechanisms And Therapeutic Interventions For Breast Cancer-Induced Fatigue And Mitochondrial Dysfunction, David Andrew Stanton
Mechanisms And Therapeutic Interventions For Breast Cancer-Induced Fatigue And Mitochondrial Dysfunction, David Andrew Stanton
Graduate Theses, Dissertations, and Problem Reports
According to the latest statistics from the National Cancer Institute (NCI), about 1 in 8 U.S. women (~13%) will develop invasive breast cancer over the course of their lifetime. This translates to an estimated 268,600 new cases of breast cancer for the year 2019, and these diagnoses will collectively make up 15% of all new cancer cases across all cancer types. The majority of these women will experience the often-debilitating symptom of breast cancer-induced fatigue. these patients often have difficulty performing normal activities of daily living, have decreased tolerance to traditional tumor-directed therapies, and have higher rates of cancer recurrence. …
Rats Genetically Selected For High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin By Upregulation Of Hepatic Biliverdin Reductase-A (Bvra) And Suppression Of Ugt1a1, Terry D. Hinds Jr., Justin F. Creeden, Darren M. Gordon, Adam C. Spegele, Steven L. Britton, Lauren G. Koch, David E. Stec
Rats Genetically Selected For High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin By Upregulation Of Hepatic Biliverdin Reductase-A (Bvra) And Suppression Of Ugt1a1, Terry D. Hinds Jr., Justin F. Creeden, Darren M. Gordon, Adam C. Spegele, Steven L. Britton, Lauren G. Koch, David E. Stec
Pharmacology and Nutritional Sciences Faculty Publications
Exercise in humans and animals increases plasma bilirubin levels, but the mechanism by which this occurs is unknown. In the present study, we utilized rats genetically selected for high capacity running (HCR) and low capacity running (LCR) to determine pathways in the liver that aerobic exercise modifies to control plasma bilirubin. The HCR rats, compared to the LCR, exhibited significantly higher levels of plasma bilirubin and the hepatic enzyme that produces it, biliverdin reductase-A (BVRA). The HCR also had reduced expression of the glucuronyl hepatic enzyme UGT1A1, which lowers plasma bilirubin. Recently, bilirubin has been shown to activate the peroxisome …
Deterministic Model Of The Voltage Dependent Anion Channel (Vdac) Kinetics, Viren Shah
Deterministic Model Of The Voltage Dependent Anion Channel (Vdac) Kinetics, Viren Shah
Theses and Dissertations
The voltage-dependent anion channel (VDAC) is a voltage gated channel residing on the outer mitochondrial membrane (OMM) that facilitates the flow of metabolites between the cytosol and mitochondria. The channel is regulated through conformational changes driven by electrostatic effects along with numerous regulatory mechanisms. The aim of this study is to mechanistically model kinetics of substrate flow through VDAC and incorporate them into existing mechanistic computational models of mitochondrial function. The resulting model is used in two ways: 1) to establish mitochondrial bioenergetics (conductance, permeability, and current/flux) under physiological conditions, and 2) to conduct perturbations simulating the effect of altered …
Inhibition Of Grk2, But Not Hsp90 Reduces Mitochondrial Superoxide And Improves Vasodilation Capacity Of Coronary Arterioles From Aged Female Rats, Michaela N Dukes, Evan P. Tracy B.S., Amanda Jo Leblanc Ph.D.
Inhibition Of Grk2, But Not Hsp90 Reduces Mitochondrial Superoxide And Improves Vasodilation Capacity Of Coronary Arterioles From Aged Female Rats, Michaela N Dukes, Evan P. Tracy B.S., Amanda Jo Leblanc Ph.D.
Undergraduate Arts and Research Showcase
Introduction: In post-menopausal women, small coronary microvessel dysfunction is the predominant heart disease presentation.There is currently no single treatment to tackle the multifactorial etiology of micro vessel dysfunction including oxidative stress, hyper constricted state, endothelial dysfunction, and blunted beta-adrenergic function. In the heart, G protein-coupled receptors (GPCRs), such as the b-adrenergic receptor (bADR) investigated in this experiment, are active in mediating vessel contractility vasodilation to facilitate blood flow. The presence of GPCR kinase 2 (GRK2), which inhibit bADRs, increase in old age and may mediate blunted capacity to vasodilate. Furthermore, GRK2 can be translocated to the mitochondria via heat shock …
Seasonal Variation In Mitochondrial Bioenergetics Of The Bluegill Sunfish, Lepomis Macrochirus, From A Shallow Midwest River, Derick Isaac Lamptey
Seasonal Variation In Mitochondrial Bioenergetics Of The Bluegill Sunfish, Lepomis Macrochirus, From A Shallow Midwest River, Derick Isaac Lamptey
Masters Theses
As average global temperature increase, the frequency and magnitude of extreme temperatures in shallow aquatic ecosystems are more ubiquitous. In order to understand how these changing thermal regimes affect aquatic ectotherms, it is essential to develop studies evaluating the response of ectotherms to seasonal fluctuating thermal regimes. Previous studies on fluctuating temperature regimes have reported an increased physiological stress leading to morphological, behavioral and biochemical adaptations. From the latter, the adaptive capacity and seasonal performance associated with optimal function of the oxidative phosphorylation system (OXPHOS) are key for species persistence. However, studies on this matter are scarce. This study explores …
Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito
Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito
Physiology Faculty Publications
Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …
Mechanisms That Limit Oxidative Phosphorylation During High-Intensity Muscle Contractions In Vivo, Miles F. Bartlett
Mechanisms That Limit Oxidative Phosphorylation During High-Intensity Muscle Contractions In Vivo, Miles F. Bartlett
Doctoral Dissertations
Skeletal muscle oxidative capacity plays a critical role in human health and disease. Although current models of oxidative phosphorylation sufficiently describe skeletal muscle energetics during moderate-intensity contractions, much is still unknown about the mechanisms that control and limit oxidative phosphorylation during high-intensity contractions. In particular, the oxygen cost of force generation is augmented during exercise at workloads above the lactate threshold. Presently, it is unclear whether this augmentation in muscle oxygen consumption is driven by increased rates of oxidative ATP synthesis (ATPOX) or by decreases in the efficiency of ATPOX due to mitochondrial uncoupling. To address this …
A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman
A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman
Graduate School of Biomedical Sciences Theses and Dissertations
Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. While remarkable progress has recently been made towards understanding the structure of mitoribosomes, the unique pathways and factors that facilitate their biogenesis remain largely unknown. This dissertation defines the physiological role of an evolutionarily conserved yeast protein called Mam33 in mitochondrial ribosome assembly. The biomedical relevance of this finding stems from the fact that mutations or changes in its expression of the human ortholog p32 result in mitochondrial dysfunction. In human patients, bi-allelic mutations cause severe multisystemic defects in mitochondrial energy metabolism, …
Bovine Milk Extracellular Vesicles (Evs) Modification Elicits Skeletal Muscle Growth In Rats, Hailey A. Parry, Christopher Brooks Mobley, Petey W. Mumford, Matthew A. Romero, Cody T. Haun, Yufeng Zhang, Paul A. Roberson, Janos Zempleni, Arny A. Ferrando, Ivan J. Vechetti Jr., John J. Mccarthy, Kaelin C. Young, Michael D. Roberts, Andreas N. Kavazis
Bovine Milk Extracellular Vesicles (Evs) Modification Elicits Skeletal Muscle Growth In Rats, Hailey A. Parry, Christopher Brooks Mobley, Petey W. Mumford, Matthew A. Romero, Cody T. Haun, Yufeng Zhang, Paul A. Roberson, Janos Zempleni, Arny A. Ferrando, Ivan J. Vechetti Jr., John J. Mccarthy, Kaelin C. Young, Michael D. Roberts, Andreas N. Kavazis
Physiology Faculty Publications
The current study investigated how bovine milk extracellular vesicles (EVs) affected rotarod performance and biomarkers of skeletal muscle physiology in young, growing rats. Twenty-eight-day Fisher 344 rats were provided an AIN-93G-based diet for 4 weeks that either remained unadulterated [EVs and RNA-sufficient (ERS; n = 12)] or was sonicated [EVs and RNA-depleted (ERD; n = 12)]. Prior to (PRE) and on the last day of the intervention (POST), animals were tested for maximal rotarod performance. Following the feeding period, the gastrocnemius muscle was analyzed at the histological, biochemical, and molecular levels and was also used to measure mitochondrial function and …
Identification Of The Alternative Oxidase Gene And Its Expression In The Copepod Tigriopus Californicus, Allison Mcdonald, Carly E. Tward, Willie Cygelfarb, Jaspreet Singh
Identification Of The Alternative Oxidase Gene And Its Expression In The Copepod Tigriopus Californicus, Allison Mcdonald, Carly E. Tward, Willie Cygelfarb, Jaspreet Singh
Biology Faculty Publications
In addition to the typical electron transport system (ETS) in animal mitochondria responsible for oxidative phosphorylation, in some species there exists an alternative oxidase (AOX) pathway capable of catalyzing the oxidation of ubiquinol and the reduction of oxygen to water. The discovery of AOX in animals is recent and further investigations into its expression, regulation, and physiological role have been hampered by the lack of a tractable experimental model organism. Our recent DNA database searches using bioinformatics revealed an AOX sequence in several marine copepods including Tigriopus californicus. This species lives in tidepools along the west coast of North …
Machine-Learning To Stratify Diabetic Patients Using Novel Cardiac Biomarkers And Integrative Genomics, Quincy A. Hathaway, Skyler M. Roth, Mark V. Pinti, Daniel C. Sprando, Amina Kunovac, Andrya J. Durr, Chris C. Cook, Garret K. Fink, Tristen B. Cheuvront, Jasmine H. Grossman, Ghadah A. Aljahli, Andrew D. Taylor, Andrew P. Giromini, Jessica L. Allen, John M. Hollander
Machine-Learning To Stratify Diabetic Patients Using Novel Cardiac Biomarkers And Integrative Genomics, Quincy A. Hathaway, Skyler M. Roth, Mark V. Pinti, Daniel C. Sprando, Amina Kunovac, Andrya J. Durr, Chris C. Cook, Garret K. Fink, Tristen B. Cheuvront, Jasmine H. Grossman, Ghadah A. Aljahli, Andrew D. Taylor, Andrew P. Giromini, Jessica L. Allen, John M. Hollander
Faculty & Staff Scholarship
Background: Diabetes mellitus is a chronic disease that impacts an increasing percentage of people each year. Among its comorbidities, diabetics are two to four times more likely to develop cardiovascular diseases. While HbA1c remains the primary diagnostic for diabetics, its ability to predict long-term, health outcomes across diverse demographics, ethnic groups, and at a personalized level are limited. The purpose of this study was to provide a model for precision medicine through the implementation of machine-learning algorithms using multiple cardiac biomarkers as a means for predicting diabetes mellitus development. Methods: Right atrial appendages from 50 patients, 30 non-diabetic and 20 …
Functional And Skeletal Muscle Impairments In Progressive Diabetic Ckd, Daniel Bittel
Functional And Skeletal Muscle Impairments In Progressive Diabetic Ckd, Daniel Bittel
Arts & Sciences Electronic Theses and Dissertations
1-in-3 persons with type 2 diabetes (T2DM) develop chronic kidney disease (CKD), which is characterized by progressive renal dysfunction leading to end-stage renal disease. In response to elevated blood glucose and systemic inflammation of diabetes, a process of active thickening of the renal glomerular basement membrane ensues with concomitant damage to the structural supports (podocytes) of the kidneyճ filtration barrier. This results in impaired renal filtration. The metabolic sequelea of T2DM and CKD also, synergistically, alter skeletal muscleճ degradative pathways, satellite cell function (muscle reparative cells), and mitochondrial health (muscle energetic machinery) -- resulting in muscle breakdown, poor muscle quality, …
Exercise Preconditioning And Tfam Overexpression Diminish Skeletal Muscle Atrophy., Nicholas Todd Theilen
Exercise Preconditioning And Tfam Overexpression Diminish Skeletal Muscle Atrophy., Nicholas Todd Theilen
Electronic Theses and Dissertations
This dissertation is an analysis of skeletal muscle atrophy and a molecular assessment of potential preventative treatments. Chapter I begins with a background of skeletal muscle atrophy along with an analysis of associated molecular pathways. Here, we discuss how skeletal muscle atrophy is the consequence of protein degradation exceeding protein synthesis and can occur when a muscle is abnormally disused. The development of therapies prior to skeletal muscle atrophy settings to diminish protein degradation is scarce and could be useful to prevent negative clinical outcomes of patients who must unload and disuse musculature over extended periods. Mitochondrial dysfunction is associated …
Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr
Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr
Theses and Dissertations
The prevalence of both Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is increasing worldwide, and the trends are unfortunately expected to continue. AD has recently been tied with mitochondrial dysfunction and insulin resistance, creating a mechanistic tie between AD and T2DM. Unfortunately, insulin resistance is often increased with aging and therefore, all individuals are at risk of brain mitochondrial dysfunction. Without proper mitochondrial function, the brain will degenerate, causing impaired cognitive function and reduced quality of life. The purpose of this study is two-fold: first, to understand the role of ceramides in insulin-induced brain mitochondrial dysfunction, and; second, …
Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr
Insulin And Ketones: Their Roles In Brain Mitochondrial Function, Sheryl Teresa Carr
Theses and Dissertations
The prevalence of both Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is increasing worldwide, and the trends are unfortunately expected to continue. AD has recently been tied with mitochondrial dysfunction and insulin resistance, creating a mechanistic tie between AD and T2DM. Unfortunately, insulin resistance is often increased with aging and therefore, all individuals are at risk of brain mitochondrial dysfunction. Without proper mitochondrial function, the brain will degenerate, causing impaired cognitive function and reduced quality of life. The purpose of this study is two-fold: first, to understand the role of ceramides in insulin-induced brain mitochondrial dysfunction, and; second, …
Cellular And Subcellular Oxidative Stress Parameters Following Severe Spinal Cord Injury, Nishant P. Visavadiya, Samir P. Patel, Jenna L. Vanrooyen, Patrick G. Sullivan, Alexander G. Rabchevsky
Cellular And Subcellular Oxidative Stress Parameters Following Severe Spinal Cord Injury, Nishant P. Visavadiya, Samir P. Patel, Jenna L. Vanrooyen, Patrick G. Sullivan, Alexander G. Rabchevsky
Spinal Cord and Brain Injury Research Center Faculty Publications
The present study undertook a comprehensive assessment of the acute biochemical oxidative stress parameters in both cellular and, notably, mitochondrial isolates following severe upper lumbar contusion spinal cord injury (SCI) in adult female Sprague Dawley rats. At 24 h post-injury, spinal cord tissue homogenate and mitochondrial fractions were isolated concurrently and assessed for glutathione (GSH) content and production of nitric oxide (NO•), in addition to the presence of oxidative stress markers 3-nitrotyrosine (3-NT), protein carbonyl (PC), 4-hydroxynonenal (4-HNE) and lipid peroxidation (LPO). Moreover, we assessed production of superoxide (O2•-) and hydrogen peroxide (H2O …
Temperature-Dependent Alterations Of Brown Adipose Tissue Metabolism During Hibernation In The Thirteen-Lined Ground Squirrel, Ictidomys Tridecemlineatus., Sarah V. Mcfarlane
Temperature-Dependent Alterations Of Brown Adipose Tissue Metabolism During Hibernation In The Thirteen-Lined Ground Squirrel, Ictidomys Tridecemlineatus., Sarah V. Mcfarlane
Electronic Thesis and Dissertation Repository
Brown adipose tissue (BAT) is the major thermogenic tissue in small eutherian mammals. In hibernators, seasonal modifications of BAT are well documented but little is known about its functional regulation during hibernation. BAT metabolism is activated by sympathetic stimulation, so I hypothesized that further regulation at the mitochondrial level, as seen in other hibernator tissues, would be of little advantage. Contrary to my predictions, respiration rates of BAT mitochondria isolated from torpid thirteen-lined ground squirrels were suppressed by up to 62% compared with rates from individuals that aroused to interbout euthermia (IBE), when measured at 37°C. At 10°C, however, these …
Neofunctionalization Of Dual-Targeted Plant Organelle Dna Replication Proteins
Neofunctionalization Of Dual-Targeted Plant Organelle Dna Replication Proteins
Journal of Undergraduate Research
Neofunctionalization is the process by which genes gain a new or modified function as a result of gene duplication and modification of one or more of the new genes. This exciting area of research helps explain the diversification of protein functions in cells. The number of documented examples has increased in recent years in all classes of organisms (Deng et al., 2010; Han et al. 2011; Cannela et al. 2014; Sakuma et al. 2013; Zhang et al. 2014). In some cases a protein that was previously thought to function in only one cellular compartment has been shown to also function …
A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun
A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun
Theses and Dissertations
Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …
Nanosecond Pulsed Platelet-Rich Plasma (Nsprp) Improves Mechanical And Electrial Cardiac Function Following Myocardial Reperfusion Injury, Barbara Y. Hargrave, Frency Varghese, Nektarios Barabutis, John Catravas, Christian Zemlin
Nanosecond Pulsed Platelet-Rich Plasma (Nsprp) Improves Mechanical And Electrial Cardiac Function Following Myocardial Reperfusion Injury, Barbara Y. Hargrave, Frency Varghese, Nektarios Barabutis, John Catravas, Christian Zemlin
Medical Diagnostics & Translational Sciences Faculty Publications
Ischemia and reperfusion (I/R) of the heart is associated with biochemical and ionic changes that result in cardiac contractile and electrical dysfunction. In rabbits, platelet-rich plasma activated using nanosecond pulsed electric fields (nsPRP) has been shown to improve left ventricular pumping. Here, we demonstrate that nsPRP causes a similar improvement in mouse left ventricular function. We also show that nsPRP injection recovers electrical activity even before reperfusion begins. To uncover the mechanism of nsPRP action, we studied whether the enhanced left ventricular function in nsPRP rabbit and mouse hearts was associated with increased expression of heat-shock proteins and altered mitochondrial …
Skeletal Muscle Lipid Metabolism And Markers Of Insulin Resistance In Young Male Low Birth Weight Offspring In Combination With A Postnatal Western Diet, Kristyn Pamela Dunlop
Skeletal Muscle Lipid Metabolism And Markers Of Insulin Resistance In Young Male Low Birth Weight Offspring In Combination With A Postnatal Western Diet, Kristyn Pamela Dunlop
Electronic Thesis and Dissertation Repository
Low birth weight offspring are at increased risk for developing metabolic syndrome in later life, specifically its precursor, insulin resistance (IR). Reduced mitochondrial lipid metabolism is implicated in IR pathogenesis, promoting accumulation of acylcarnitines, and potentiating alterations in phosphorylation status of insulin signaling intermediates. While high-energy Western diets are classically implicated in IR progression, the in utero environment was recently highlighted as a major programming mechanism of later life IR. Using a guinea pig model of placental insufficiency, we investigated how an adverse in utero environment impacts later life mitochondrial lipid metabolism and IR progression, as well as its interaction …
Cigarette Smoke Increases Cardiomyocyte Ceramide Accumulation And Inhibits Mitochondrial Respiration, Trevor Stanley Tippetts
Cigarette Smoke Increases Cardiomyocyte Ceramide Accumulation And Inhibits Mitochondrial Respiration, Trevor Stanley Tippetts
Theses and Dissertations
Cigarette smoking is a common and lethal worldwide habit, with considerable mortality stemming from its deleterious effects on heart function. While current theories posit altered blood lipids and fibrinogen metabolism as likely mediators, none have explored the role of the sphingolipid ceramide in exacerbating heart function with smoke exposure. Ceramide production is a consequence of cigarette smoke in the lung, and considering ceramide's harmful effects on mitochondrial function, we sought to elucidate the role of ceramide in mediating smoke-induced altered heart mitochondrial respiration. Lung cells were exposed to cigarette smoke extract and heart cells were exposed to the lung-cell conditioned …
The Role Of Receptors For Advanced Glycation End-Products (Rage) And Ceramide In Cardiovascular Disease, Michael Bruce Nelson
The Role Of Receptors For Advanced Glycation End-Products (Rage) And Ceramide In Cardiovascular Disease, Michael Bruce Nelson
Theses and Dissertations
Type 2 diabetes and cigarette smoke exposure are associated with an increased risk of cardiovascular complications. The role of advanced glycation end-products (AGEs) is already well-established in numerous comorbidities including cardiomyopathy. Given the role of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought to determine whether ceramides could be a mediator of RAGE-induced altered heart mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes with carboxy-methyl lysine-BSA, followed by mitochondrial respiration assessment. We found that mitochondrial respiration was significantly impaired in AGE-treated cells, but not when co-treated with myriocin, an inhibitor of de novo …
Mitochondrial Therapeutics During Ischemia-Reperfusion; Modulation Of Complex I: Effect Of Metformin., Shawn Y. Sunu
Mitochondrial Therapeutics During Ischemia-Reperfusion; Modulation Of Complex I: Effect Of Metformin., Shawn Y. Sunu
Theses and Dissertations
The modulation of the electron transport during ischemia-reperfusion has been shown to be protective. We hypothesized that metformin, a Complex I inhibitor, may exhibit characteristics of a pharmacological agent that could achieve long-term therapeutic intervention against ischemia-reperfusion injury. Mitochondria were harvested from adult male mice and incubated with or without metformin at 30oC for 15 minutes, while being shaken at 300 rpm. Metformin decreased Complex I oxidative phosphorylation and Complex I activity. However, metformin also increased injury and decreased the maximum membrane potential. Even though there was a decrease in maximum membrane potential, the proton motive force (PMF) …
Metabolic Characterization Of Mpnst Cell Lines, Christopher A. Waker
Metabolic Characterization Of Mpnst Cell Lines, Christopher A. Waker
Browse all Theses and Dissertations
Malignant transformation is the process by which cells develop cancer properties. While many causes for malignant transformation are known (i.e. common genetic mutations and/or exposure to toxins or viruses), the basic requirements that allow a cell to stay alive with altered nutrient and energy requirements are just now being studied. In some tumor types malignant cells undergo changes that result in metabolic differences compared to normal cells. These can include defects in mitophagy resulting in an accumulation of dysfunctional mitochondria and/or a metabolic switch resulting in increased glycolysis, termed the Warburg effect. Increased tumor growth and metastasis have also been …
Mitochondria Dysfunction In Lung Cancer-Induced Muscle Wasting In C2c12 Myotubes, Julie B. Mclean, Jennifer S. Moylan, Francisco H. Andrade
Mitochondria Dysfunction In Lung Cancer-Induced Muscle Wasting In C2c12 Myotubes, Julie B. Mclean, Jennifer S. Moylan, Francisco H. Andrade
Physiology Faculty Publications
Aims: Cancer cachexia is a syndrome which results in severe loss of muscle mass and marked fatigue. Conditioned media from cachexia-inducing cancer cells triggers metabolic dysfunction in skeletal muscle, including decreased mitochondrial respiration, which may contribute to fatigue. We hypothesized that Lewis lung carcinoma conditioned medium (LCM) would impair the mitochondrial electron transport chain (ETC) and increase production of reactive oxygen species, ultimately leading to decreased mitochondrial respiration. We incubated C2C12 myotubes with LCM for 30 min, 2, 4, 24 or 48 h. We measured protein content by western blot; oxidant production by 2′,7′-dichlorofluorescin diacetate (DCF), 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF), and …