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The Effects Of Diesel Exhaust Particle Exposure On Adipos Mitochondrial Bioenergetics And Inflammation, Cali Elizabeth Warren
The Effects Of Diesel Exhaust Particle Exposure On Adipos Mitochondrial Bioenergetics And Inflammation, Cali Elizabeth Warren
Theses and Dissertations
Fine particulate matter (PM2.5) constitutes a significant component of ambient air pollution that has been implicated in the pathogenesis of metabolic disorders, including insulin resistance and type 2 diabetes. Among PM2.5 constituents, diesel exhaust particles (DEP) are prevalent particulates that infiltrate the bloodstream to drive systemic pathologies. The purpose of this study was to characterize the metabolic response of adipose tissue to DEP. We aimed to provide a comprehensive understanding by exploring mitochondrial bioenergetics, characterizing the inflammatory marker profile, including adipokines, and conducting a detailed histological analysis of adipocytes to provide valuable insights to the evolving understanding of the intricate …
Characterizing Stress Granule Regulation By Pas Kinase, Ataxin-2 And Ptc6 And Investigating The Lifespan Of Covid-19 Virus On Currency, Colleen R. Newey
Characterizing Stress Granule Regulation By Pas Kinase, Ataxin-2 And Ptc6 And Investigating The Lifespan Of Covid-19 Virus On Currency, Colleen R. Newey
Theses and Dissertations
The protein Ataxin-2 is a known positive regulator of stress granules in humans, mice and yeast (known as yeast PBP1). Due to the role that stress granules play in diseases including Amyotrophic Lateral Sclerosis (ALS) and cancer, this thesis investigates the role of Ataxin-2 and its protein binding partners in stress granule development and its effects on various metabolic phenotypes of the cell. PAS kinase is a sensory protein kinase, conserved from yeast to man, which regulates respiration and lipid biosynthesis. Our lab discovered that PAS kinase phosphorylates and activates Ataxin-2 in yeast, and that PAS kinase overexpression enhances localization …
Evolution And Selection: From Suppression Of Metabolic Deficiencies To Bacteriophage Host Range And Resistance, Daniel Kurt Arens
Evolution And Selection: From Suppression Of Metabolic Deficiencies To Bacteriophage Host Range And Resistance, Daniel Kurt Arens
Theses and Dissertations
The evolution and adaptation of microorganisms is so rapid it can be seen in the time frame of days. The root cause for their evolution comes from selective environmental pressures that see organisms with beneficial mutations survive otherwise deadly encounters or outperform members of its population who fail to adapt. This does not always result in strict improvement of the individual as in the case of antibiotic resistant bacteria who often display fitness tradeoffs to avoid death (see Reviews [1-3]). For example, when an ampicillin resistance gene (ampC) containing plasmid that is occasionally found in the wild was transformed into …
Effects Of Curcumin And Ursolic Acid On The Mitochondrial Coupling Efficiency And Hydrogen Peroxide Emission Of Intact Skeletal Myoblasts, Daniel J. Tueller
Effects Of Curcumin And Ursolic Acid On The Mitochondrial Coupling Efficiency And Hydrogen Peroxide Emission Of Intact Skeletal Myoblasts, Daniel J. Tueller
Theses and Dissertations
Curcumin is a natural compound that improves blood glucose management. While some evidence from isolated mitochondria indicates that curcumin uncouples electron transport from oxidative phosphorylation, the effects of curcumin on mitochondrial respiration and hydrogen peroxide emission in intact skeletal muscle cells are not known. By assessing rates of oxygen consumption, we demonstrated for the first time that curcumin (40 µM) reduced the mitochondrial coupling efficiency (percentage of oxygen consumption that supports ATP synthesis) of intact skeletal muscle cells. A 30-minute incubation with curcumin decreased mitochondrial coupling efficiency by 17.0 ± 0.4% relative to vehicle (p < 0.008). Curcumin also decreased the rate of hydrogen peroxide emission by 43 ± 13% compared to vehicle (p < 0.05). Analysis of cell respiration in the presence of curcumin revealed a 40 ± 4% increase in the rate of oxygen consumption upon curcumin administration (p < 0.05 compared to vehicle). In additional experiments, no difference in mitochondrial coupling efficiency was observed between vehicle- and curcumin-pretreated cells after permeabilization of cell membranes (p > 0.7). The possibility of synergistic …
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, …
Insulin Treatment Increases Myocardial Ceramide Accumulation And Disrupts Cardiometabolic Function, Aimee Elizabeth Hodson
Insulin Treatment Increases Myocardial Ceramide Accumulation And Disrupts Cardiometabolic Function, Aimee Elizabeth Hodson
Theses and Dissertations
Prevalence of diabetes, especially type 2 diabetes mellitus (T2DM) is increasing worldwide. Millions of people are already affected by T2DM and estimates predict over half a billion people will likely be suffering from the disease by 2030. T2DM is associated with an increased risk of developing cardiovascular disease. Cardiovascular dysfunction is the leading cause of mortality among type 2 diabetics. Treatment for T2DM has changed over time. Though it was once known as insulin independent, a large portion of type 2 diabetics are now treated with insulin injections. However, type 2 diabetics treated with insulin are more likely to suffer …
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 …
The Role Of Ceramides In Mediating Endotoxin-Induced Mitochondrial Disruption, Melissa Ellen Hansen
The Role Of Ceramides In Mediating Endotoxin-Induced Mitochondrial Disruption, Melissa Ellen Hansen
Theses and Dissertations
Ceramides are sphingolipids that serve as important second messengers in an increasing number of stress-induced pathways. Ceramide has long been known to affect the mitochondria, altering both morphology and physiology. Lipopolysaccharide (LPS) is a prevalent circulating inflammatory agent in obesity, potentially mediating some of the pathologies associated with weight gain. Given previous findings of TLR4-mediated ceramide accrual and ceramide-mediated mitochondrial disruption, we questioned whether ceramide is necessary for LPS-induced mitochondrial disruption. We found that LPS treatment increased gene transcript levels of ceramide synthesis enzymes and mitochondrial fission proteins and increased ceramide content in cultured myotubes and in mouse tissue. Mitochondrial …
Identification Of The Binding Partners For Hspb2 And Cryab Reveals Myofibril And Mitochondrial Protein Interactions And Non-Redundant Roles For Small Heat Shock Proteins, Kelsey Murphey Langston
Identification Of The Binding Partners For Hspb2 And Cryab Reveals Myofibril And Mitochondrial Protein Interactions And Non-Redundant Roles For Small Heat Shock Proteins, Kelsey Murphey Langston
Theses and Dissertations
Small Heat Shock Proteins (sHSP) are molecular chaperones that play protective roles in cell survival and have been shown to possess chaperone activity. As such, mutations in this family of proteins result in a wide variety of diseases from cancers to cardiomyopathies. The sHSPs Beta-2 (HspB2) and alpha-beta crystalline (CryAB) are two of the ten human sHSPs and are both expressed in cardiac and skeletal muscle cells. A heart that cannot properly recover or defend against stressors such as extreme heat or cold, oxidative/reductive stress, and heavy metal-induced stress will constantly struggle to maintain efficient function. Accordingly, CryAB is required …
Characterization Of The Cellular And Organellar Dynamics That Occur With A Partial Depletion Of Mitochondrial Dna When Arabidopsis Organellar Dna Polymerase Ib Is Mutated, John D. Cupp
Theses and Dissertations
Plant mitochondrial genomes are large and complex, and the mechanisms for maintaining mitochondrial DNA (mtDNA) remain unclear. Arabidopsis thaliana has two DNA polymerase genes, polIA and polIB, that have been shown to be dual localized to mitochondria and chloroplasts but are unequally expressed within primary plant tissues involved in cell division or cell expansion. PolIB expression is observed at higher levels in both shoot and root apexes, suggesting a possible role in organelle DNA replication in rapidly dividing or expanding cells. It is proposed that both polIA and polIB are required for mtDNA replication under wild type conditions. An Arabidopsis …
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 …
Organellar Dna Polymerases Gamma I And Ii In Arabidopsis Thaliana, Jeffrey M. Brammer
Organellar Dna Polymerases Gamma I And Ii In Arabidopsis Thaliana, Jeffrey M. Brammer
Theses and Dissertations
Plants have two organelles outside the nucleus which carry their own DNA, mitochondria and chloroplasts. These organelles are descendants of bacteria that were engulfed by their host according to the endosymbiotic theory. Over time, DNA has been exchanged between these organelles and the nucleus. Two polymerases, DNA Polymerases Gamma I and II, are encoded in the nucleus and remain under nuclear control, but are transported into the mitochondria and chloroplasts. DNA polymerases gamma I and II are two organelle polymerases which have been studied through sequence analysis and shown to localize to both mitochondria and chloroplasts. Little has been done …
Effects Of Endurance Training On The Ampk Response To Exercise., David Gerald Chesser
Effects Of Endurance Training On The Ampk Response To Exercise., David Gerald Chesser
Theses and Dissertations
Activation of AMP-activated protein kinase (AMPK) results in the upregulation of several intracellular systems which help to prepare a cell for a high energy challenge. The magnitude of the AMPK response to a 10 min bout of exercise has been found to decrease in red quadriceps (RQ) following training, while putative AMPK roles seem to be maintained; specifically, the biogenesis of mitochondria and higher levels of hexokinase II and glucose transporter 4 (GLUT4). If the AMPK response to exercise is responsible in part for these adaptations, how can they be maintained if the AMPK response is attenuated? The purpose of …