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Full-Text Articles in Life Sciences
Osteoarthritis And Cartilage Insult: Elucidation Of Molecular Interplay And Attempted Interventions, Brandon James Rose
Osteoarthritis And Cartilage Insult: Elucidation Of Molecular Interplay And Attempted Interventions, Brandon James Rose
Theses and Dissertations
Osteoarthritis (OA) is a common and incapacitating joint disease beginning with breakdown of articular cartilage and extending into subchondral bone. At present, the processes through which the disease occurs are poorly understood, and interventions are limited to pain relief and eventual joint replacement. OA is commonly associated with obesity and corresponding pathologies, and as OA is demonstrably not a product of passive erosion of cartilage over time or under increased loads there must needs be some other mechanistic link between the two conditions. We hypothesize that the production of ceramides, a hallmark of the insulin resistance syndrome underlying many obesity-related …
A Comprehensive Comparison Of Teratogenic Compounds Known To Induce Neural Tube Defects In The Chicken Embryo, Micah Marie Ross
A Comprehensive Comparison Of Teratogenic Compounds Known To Induce Neural Tube Defects In The Chicken Embryo, Micah Marie Ross
Theses and Dissertations
One of the first embryonic structures generated during early human development is the neural tube. The embryonic process of neurulation, including neural tube closure, is necessary for proper brain and spinal cord development, whereas improper closure leads to neural tube defects including anencephaly, spina bifida, and craniorachischisis. The mechanism by which these defects occur is unknown, but some evidence suggest that redox disruption may play a role. Cellular redox state is important in regulating key processes during neural tube closure, including differentiation, proliferation, gene expression, and apoptosis. This study aims to determine whether redox potential shifts and these key processes …
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 …
Hmgb1 And Ceramides: Potential Mediators Of Cigarette Smoke-Induced Metabolic Dysfunction, Mikayla Orton Thatcher
Hmgb1 And Ceramides: Potential Mediators Of Cigarette Smoke-Induced Metabolic Dysfunction, Mikayla Orton Thatcher
Theses and Dissertations
While cigarette smoking is a common-knowledge way to stay lean, it has long been known as a risk factor for diabetes and obesity. Here we establish that smoking causes fat gain and metabolic disruption in mice, effects which are exacerbated by a high-fat, high-sugar diet. We found that smoke exposure increases levels of ceramide—the lipid responsible for diet-induced insulin resistance—and that blocking ceramide production with the pharmacological inhibitor myriocin restored insulin sensitivity, stopped weight gain, and rescued mitochondrial respiration in vivo and in vitro.We also sought to assess the impact of the RAGE ligand HMGB1 on skeletal muscle metabolism. We …
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 …
Ipla2Β, Alternative Splicing And Apoptosis Of Pancreatic Islets, Bhargavi Emani
Ipla2Β, Alternative Splicing And Apoptosis Of Pancreatic Islets, Bhargavi Emani
Theses and Dissertations
Ceramides are bioactive lipids that can promote splicing of apoptosis-related genes, including caspase 9 and BCL-x. A recent study demonstrated that expression of neutral sphingomyelinase (NSMase), an enzyme that hydrolyzes sphingomyelins to generate ceramide, is regulated by Group VIA phospholipase A2 (iPLA2β)-dependent mechanism during β-cell apoptosis. This prompted us to hypothesize that iPLA2 is upstream of ceramide generation in the process regulating splicing of apoptotic genes. To test this, Jurkat T cells were treated with the selective inhibitor of iPLA2β, bromoenol lactone (BEL), RNA was isolated and converted to cDNA, and caspase 9 and BCL-x mRNA viii species were amplified …
Sphingolipid-Induced Activation Of The Volume-Sensitive Cl− Current Is Mediated By Mitochondrial Reactive Oxygen Species, Frank Raucci
Sphingolipid-Induced Activation Of The Volume-Sensitive Cl− Current Is Mediated By Mitochondrial Reactive Oxygen Species, Frank Raucci
Theses and Dissertations
Swelling-activated Cl− current (ICl,swell) is an outwardly-rectifying current that plays an important role in cardiac electrical activity, cellular volume regulation, apoptosis, and acts as a potential effector of mechanoelectrical feedback. Persistent activation of ICl,swell has been observed in a number of models of cardiovascular disease. Previously we showed that angiotensin II (Ang II), endothelin-1 (ET-1), endothelial growth factor receptor (EGFR), and reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and mitochondria are involved in the activation of ICl,swell by both osmotic swelling and Beta1 integrin stretch. Sphingolipid metabolism is modulated in several cardiopathologies and because sphingolipids are bioactive lipids …
Structure-Activity Studies Of Glycosphingolipids As Antigens Of Natural Killer T Cells, Randal Donald Goff
Structure-Activity Studies Of Glycosphingolipids As Antigens Of Natural Killer T Cells, Randal Donald Goff
Theses and Dissertations
Glycosphingolipids (GSLs), composed of a polar saccharide head and a lipophilic ceramide tail, are ubiquitous components of the plasma membrane of eukaryotic cells. They serve in many regulatory capacities and have antigenic properties towards natural killer T (NKT) cells of the innate immune system. Critical to the recognition of glycosylceramides by NKT cells are antigen presenting cells (APC), such as dendritic cells, which are responsible for binding, processing, and delivery of ligands to these lymphocytes. This event is mediated by CD1d, a major histocompatibility complex-like protein expressed on the surface of APCs, which binds GSL antigens by the ceramide moiety …
Identification Of The Rna Cis-Elements That Interact With Srp30a To Regulate The Alternative Splicing Of Caspase 9 Pre-Mrna, Prabhat Mukerjee
Identification Of The Rna Cis-Elements That Interact With Srp30a To Regulate The Alternative Splicing Of Caspase 9 Pre-Mrna, Prabhat Mukerjee
Theses and Dissertations
Studies have shown that the alternative splicing of caspase 9 and the phospho-status of SR proteins, a conserved family of splicing factors, are regulated by chemotherapy and de novo ceramide via the action of protein phosphatase-1 (PP1). Two RNA splice variants are derived from the caspase 9 gene, pro-apoptotic caspase 9a and anti-apoptotic caspase 9b, via alternative splicing by either the inclusion or exclusion of an exon 3, 4, 5, and 6 cassette. In this study, the link between SR proteins and the alternative splicing of caspase 9 was established. Sequence analysis of the exon 3, 4, 5, and 6 …