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Electronic Theses and Dissertations

University of Louisville

2014

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Full-Text Articles in Life Sciences

Effects Of Step Training On The Kidneys Following Spinal Cord Injury In Rats., Pradeepa Poudyal Dec 2014

Effects Of Step Training On The Kidneys Following Spinal Cord Injury In Rats., Pradeepa Poudyal

Electronic Theses and Dissertations

Detrusor-sphincter dyssynergia after chronic spinal cord injury (SCI) leads to over-distention, high bladder pressures and vesico-ureteric reflux into the kidney, resulting in repeated infections and pyelonephritis. Given the importance/limited knowledge of SCI effects on the upper urinary tract, this study assessed expression of two proteins in the kidneys of contused (T9) male rats relative to controls that are indicative of tissue stress/damage (TGFβ, CD11b). The impact of two therapeutic rehabilitation strategies, 60 minutes of step training and general exercise, was then assessed on these protein levels relative to non-trained SCI controls, plus the effectiveness of a shorter training duration (30 …


The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988- Dec 2014

The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988-

Electronic Theses and Dissertations

The work presented in this dissertation outlines the role of stem cells in the remodeling of adipose tissue under conditions of nutrient excess. Obesity-induced variations in adipose tissue stem cell distribution were uncovered by analysis of the stromal vascular fraction isolated from mice fed a high fat diet for several weeks. Bone marrow cell transplantation was used to determine the derivation of progenitor cells found in adipose tissue; and supplementation of depleted progenitor cell populations achieved via direct cell transplantation, helped to determine the contribution of these progenitor cells to the remodeling process. The dissertation is presented in five chapters …


Troglitazone Suppresses Glutamine Metabolism And Tumor Cell Growth Through A Ppar-Independent Mechanism., Miriam R. Reynolds 1965- Dec 2014

Troglitazone Suppresses Glutamine Metabolism And Tumor Cell Growth Through A Ppar-Independent Mechanism., Miriam R. Reynolds 1965-

Electronic Theses and Dissertations

In tumor cells, glutamine metabolism provides anaplerotic carbon for the TCA cycle, fatty acid synthesis, and precursors for the production of nucleotides and glutathione. This metabolic alteration is primarily driven by disruptions in oncogenic or tumor suppressor function and results in glutamine dependency for tumor cell survival. Troglitazone, a PPARγ agonist, has been reported to alter glutamine metabolism. This thesis project addresses whether troglitazone treatment could disrupt glutamine metabolism in glutamine-dependent tumor cells. Results obtained with troglitazone treatment include: dose-dependent inhibition of cell proliferation, glutamine uptake, glutaminolytic protein expression, steady-state ATP levels, and glutamine carbon flux into the TCA cycle. …


A Mechanism For Trif Adaptor-Biased Signaling By Toll-Like Receptor 4., Joseph Peterson Kolb Dec 2014

A Mechanism For Trif Adaptor-Biased Signaling By Toll-Like Receptor 4., Joseph Peterson Kolb

Electronic Theses and Dissertations

Host cells respond to bacterial lipid A through Toll-like receptor 4 (TLR4). Activation of TLR4 by lipid A triggers a response that involves two main adaptor proteins, MyD88 and TRIF. MyD88-dependent gene expression is associated with proinflammatory protein production, while TRIF-dependent gene expression is essential for optimal activation of adaptive immunity by antigen-presenting cells. Detoxified, monophosphoryl lipid A agonists (MPLA or synthetic MLA) were previously suggested to elicit TRIF-biased TLR4 signaling; that is, induction of weaker MyD88-associated gene expression but relatively intact TRIF-dependent gene expression when compared to fully active diphosphoryl lipid A (lipid A). In this work, we explored …


Enzyme Kinetics : 6-Phosphofructo-2-Kinase/2,6-Bisphosphatase., Jennifer Clark Dec 2014

Enzyme Kinetics : 6-Phosphofructo-2-Kinase/2,6-Bisphosphatase., Jennifer Clark

Electronic Theses and Dissertations

Altered energy metabolism is an established hallmark of cancer cells. Fructose-2,6-bisphosphate is an allosteric activator of glycolysis and its concentration in a cell is dictated by the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) family of bifunctional enzymes. The PFKFB family of enzymes are characterized by their different kinase: bisphosphatase activities and were originally determined to be tissue-specific. More recent data however suggest that multiple isoforms are co-expressed in both normal and neoplastic tissues. PFKFB4 is highly expressed in human cancer, strongly induced by hypoxia, and required for the survival of cancer cells. However, it remains unclear whether the kinase or phosphatase activity of human …


Modulation Of Host Polyubiquitination By The Ankb F-Box Protein Of Legionella Pneumophila., William M. Bruckert Dec 2014

Modulation Of Host Polyubiquitination By The Ankb F-Box Protein Of Legionella Pneumophila., William M. Bruckert

Electronic Theses and Dissertations

Legionella pneumophila is a facultative intracellular pathogen that infects a wide array of protozoan hosts and human alveolar macrophages. L. pneumophila is dependent on a functional Dot/Icm type IVB secretion system that translocates bacterial effector proteins into the host cell cytosol. L. pneumophila genomes encode more than 250 effector proteins, many of which inhibit host cellular processes to form a favorable niche termed the Legionella-containing vacuole (LCV). The eukaryotic-like Dot/Icm translocated effector AnkB contains two eukaryotic-like ankyrin protein-protein interacting domains, one eukaryotic-like F- box domain and an eukaryotic C-terminal CaaX motif. Immediately following attachment of extracellular bacteria, AnkB is translocated …


Evaluating The Effects Of Aroclor 1260 In Non-Alcoholic Fatty Liver Disease : The Role Of Xenobiotic Receptors., Banrida Wahlang Dec 2014

Evaluating The Effects Of Aroclor 1260 In Non-Alcoholic Fatty Liver Disease : The Role Of Xenobiotic Receptors., Banrida Wahlang

Electronic Theses and Dissertations

Polychlorinated biphenyls (PCBs) are persistent environmental toxicants, present in 100% of US adults and dose-dependently associated with nonalcoholic fatty liver disease (NAFLD) in epidemiologic studies. PCBs are predicted to interact with receptors previously implicated in xenobiotic/energy metabolism and NAFLD. These receptors include the aryl hydrocarbon receptor (AhR), pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptors (PPARs), liver-X-receptor and farnesoid-X-receptor. This study evaluated the hepatic effects of the PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity. Male C57Bl/6J mice were fed a control or 42% high fat diet (HFD) …


Mechanistic Investigations Of Pseudouridine Synthases : A Surprising Glycal Intermediate Lies On The Reaction Pathway., Govardhan Reddy Veerareddygari Dec 2014

Mechanistic Investigations Of Pseudouridine Synthases : A Surprising Glycal Intermediate Lies On The Reaction Pathway., Govardhan Reddy Veerareddygari

Electronic Theses and Dissertations

Pseudouridine synthases (ΨSs) catalyze the isomerization of uridine (U) in RNA to pseudouridine (Ψ), which is the most common post-transcriptional modification in RNAs and is ubiquitous within all three domains of life. ΨSs are classified into six different families based on sequence alignments and have a universally conserved aspartic acid residue (‘conserved Asp’ for simplicity) that is absolutely essential for activity. RNA containing 5-fluorouridine ([F5U]RNA) has been used as a mechanistic probe. Upon incubation with [F5U]RNA, TruA and RluA get irreversibly inhibited and appear in a protein-RNA adduct band on denaturing PAGE gels, which is consistent with the ‘Michael mechanism’ …


Boundary Contour Based Surface Representation., Yong Su Dec 2014

Boundary Contour Based Surface Representation., Yong Su

Electronic Theses and Dissertations

We receive most information about our surrounding space and objects through the eyes. To reconstruct the 3D space and objects in the visual system from the 2D retinal images, surface representation must be a critical intermediate stage in the visual processing stream. It is hypothesized in the dissertation that the visual system represents textured surface by a border-to-interior strategy: boundary contours would be encoded first and then border-ownership assignments would be resolved. This process would solve the related problems such as figure-ground segregation, surface depth relationship, occlusion, transparency, etc. As a result, the boundary contours of the surfaces would be …


Post-Transcriptional Regulation Of The Type Iia Sodium-Phosphate Cotransporter By Parathyroid Hormone., Rebecca Dale Murray Dec 2014

Post-Transcriptional Regulation Of The Type Iia Sodium-Phosphate Cotransporter By Parathyroid Hormone., Rebecca Dale Murray

Electronic Theses and Dissertations

The type IIa sodium-phosphate cotransporter (Npt2a) is expressed in the apical membrane of the renal proximal tubule and is responsible for the reabsorption of the majority of the filtered load of phosphate. Parathyroid hormone (PTH) is secreted by the parathyroid gland in response to a decrease in serum calcium or an increase in serum phosphorus, and acutely induces phosphaturia through the rapid stimulation of endocytosis of Npt2a and its subsequent lysosomal degradation. Chronic PTH stimulation leads to sustained phosphaturia, but the mechanisms for the chronic regulation of Npt2a by PTH remain unclear. We hypothesize that PTH decreases Npt2a mRNA levels …


Earthworm, Microbial Biomass, And Leaf Litter Decay Responses After Invasive Honeysuckle Shrub Removal From Urban Woodlands., Robert Preston Pipal Dec 2014

Earthworm, Microbial Biomass, And Leaf Litter Decay Responses After Invasive Honeysuckle Shrub Removal From Urban Woodlands., Robert Preston Pipal

Electronic Theses and Dissertations

Invasive species are one of the leading causes of biodiversity loss and their presence can significantly impact the structure and function of native ecosystems. In this dissertation, the impacts of the invasive honeysuckle shrub, Lonicera maackii, on exotic earthworm populations, leaf litter decay responses, and inorganic and organic nutrient pools in an urban woodland park are assessed. Chapter 1 provides a brief review of honeysuckle's effects on forest ecosystems. Chapter 2 describes honeysuckle’s effects on exotic earthworm populations and the seasonal importance of macroinvertebrates to leaf litter decomposition in urban woodlands. This study revealed that L. maackii promoted higher exotic …


The Effect Of A Controlled Frequency Breath Holding Training Program On Running Economy Among Elite College Swimmers., Patrick Sims 1988- Dec 2014

The Effect Of A Controlled Frequency Breath Holding Training Program On Running Economy Among Elite College Swimmers., Patrick Sims 1988-

Electronic Theses and Dissertations

Running economy (RE) is the amount of oxygen consumed while running at a submaximal intensity. Along with aerobic capacity (VO2max), RE is an important predictor of running performance. Little research has investigated changes in RE with restricted breathing training [i.e. controlled breath-holding (CFB)] during exercise. RE may improve ~6% amongst a novice swimming cohort through CFB training, but this has not been established in elite swimmers. The purpose was to further establish that CFB training (16 sessions of 12 x 50-m with ~15 seconds rest between each 50-m, using only ~2 breaths per 50-m) can improve RE in 25 elite …


Modulation Of The Ovarian Cancer Humoral Response By Tumor-Derived Exosomes., Carolyn Denise Roberson Dec 2014

Modulation Of The Ovarian Cancer Humoral Response By Tumor-Derived Exosomes., Carolyn Denise Roberson

Electronic Theses and Dissertations

The pathogenesis of epithelial ovarian cancer is complicated by its diagnosis during the latter stages of the disease resulting from lack of symptoms or from presence of symptoms that mimic other conditions. Because of the often fatal prognosis by the time of actual detection, efforts are being made to better understand the host immune response to ovarian cancer. In this study, the contributions of the humoral immune response were investigated by focusing on the role of tumor-derived exosomes and their ability to modulate humoral immune responses. First, ovarian cancer patient-derived free circulating antibodies were investigated for immunoreactivity to patient antigen. …


Mirna-21 Has Anti-Inflammatory Effects In The Macrophage Response To Peritonitis., Rebecca Elise Barnett Aug 2014

Mirna-21 Has Anti-Inflammatory Effects In The Macrophage Response To Peritonitis., Rebecca Elise Barnett

Electronic Theses and Dissertations

This project investigated the role of miRNA-21 in the macrophage response to peritonitis; with the goal of understanding whether the associated mechanism has potential benefits in the clinical treatment of peritonitis. A novel therapeutic intervention in the treatment of peritonitis could modulate the host immune response to decrease an exaggerated pro-inflammatory innate response and then prevent or ameliorate the development of sepsis and organ failure. We found the following: 1. MiRNA-21 expression increases in peritoneal macrophages after lipopolysaccharide (LPS) stimulation. 2. Over expression of miRNA-21 decreases TNF-a secretion from macrophages after LPS stimulation. Suppression of miRNA-21 expression results in increased …


Biophysical And Computational Investigations Into G-Quadruplex Structural Polymorphism And Interaction With Small Molecules., Huy Tuan Le Aug 2014

Biophysical And Computational Investigations Into G-Quadruplex Structural Polymorphism And Interaction With Small Molecules., Huy Tuan Le

Electronic Theses and Dissertations

In the cell, guanine-rich nucleic acids can self-assemble into unique four stranded tertiary structures known as G-quadruplexes. G-quadruplex formation in the telomere leads inhibits telomerase, an enzyme activated in cancer cells to maintain the telomere and allowing for cancer cells to achieve immortality. G-quadruplex formation in the promoters and 5’-untranslated regions regulates the expression of many oncogenes. Furthermore, G-quadruplex formation during cellular replication promotes genomic instability, a characteristic which enables tumor development. Because of their implication in cancer, G-quadruplex structures have emerged as attractive drug targets for anti-tumor therapeutics. In the current dissertation work, we present three experimental approaches to …


Il-12 Induced Modulation Of Tumor Derived Myeloid Cell Inflammatory Responsiveness., Courtney Jetun Mitchell Aug 2014

Il-12 Induced Modulation Of Tumor Derived Myeloid Cell Inflammatory Responsiveness., Courtney Jetun Mitchell

Electronic Theses and Dissertations

Tumor infiltrating and tumor associated myeloid cells (TIMs and TAMs) elaborate an array of factors that promote tumor growth and metastasis. IL-12, a potent inflammatory cytokine has been shown to induce regression of many cancers. We hypothesize that IL-12 augments the ability of TIMs and TAMs to respond to inflammatory stimuli providing a window in which these stimuli are more likely to promote tumor destruction. Related to this hypothesis, we asked two questions: (1) Does IL-12 directly change signaling events associated with inflammatory signal transduction? (2) Is IFN? required for the entirety of IL-12 induced enhancement of the response of …


Genetic And Mechanistic Analysis Of Rat Mammary Cancer Susceptibility., Jennifer Sanders Aug 2014

Genetic And Mechanistic Analysis Of Rat Mammary Cancer Susceptibility., Jennifer Sanders

Electronic Theses and Dissertations

Breast cancer is a complex disease, which is influenced by genetic, epigenetic and environmental components. Genetic susceptibility to breast cancer is made up of high, moderate and low penetrance alleles. High and moderate penetrance alleles are rare and constitute only a small percentage of the genetic susceptibility. Most variation in genetic susceptibility is controlled by low- penetrance, common polymorphisms. Comparative genetics uses model organisms to study human disease. Rat strains exhibit different susceptibility phenotypes to chemical induced carcinogenesis. The Wistar-Furth (WF) rat strain is susceptible to chemically induced mammary carcinogenesis, while the Wistar-Kyoto (WKy) and Copenhagen (COP) rat strains are …


Statistical Methods For Assessing Treatment Effects For Observational Studies., Kristopher C. Gardner 1984- May 2014

Statistical Methods For Assessing Treatment Effects For Observational Studies., Kristopher C. Gardner 1984-

Electronic Theses and Dissertations

Though randomized clinical (RCTs) trials are the gold standard for comparing treatments, they are often infeasible or exclude clinically important subjects, or generally represent an idealized medical setting rather than real practice. Observational data provide an opportunity to study practice-based evidence, but also present challenges for analysis. Traditional statistical methods which are suitable for RCTs may be inadequate for the observational studies. In this project, four of the most popular statistical methods for observational studies: ANCOVA, propensity score matching, regression with the propensity score as a covariate, and instrumental variables (IV) are investigated through application to MarketScan insurance claims data. …


Augmentation Of Ras-Induced Cell Transformation : A New Role For Mir-200a In Malignancy., Lindsey Erin Becker May 2014

Augmentation Of Ras-Induced Cell Transformation : A New Role For Mir-200a In Malignancy., Lindsey Erin Becker

Electronic Theses and Dissertations

Cancer is a multistep disease that begins with malignant cell transformation and frequently culminates in metastasis and death. MicroRNAs (miRNAs) are small regulatory 21-25-nt RNA molecules and are frequently deregulated in cancer. The majority of miRNAs are estimated to be co-expressed with neighboring miRNAs as clusters. Many miRNA clusters coordinately regulate multiple members of cellular signaling pathways or protein interaction networks. miR-200a is a member of the miR-200 family, which are known to be strong inhibitors of the epithelial to mesenchymal transition. As such, the tumor suppressive role of miR-200a in oncogenesis has been well studied; however, recent studies have …


Mechanisms Of Action And Co-Optive Evolution For Hypervariable Courtship Pheromones In Plethodontid Salamanders., Wilburn Beau Wilburn May 2014

Mechanisms Of Action And Co-Optive Evolution For Hypervariable Courtship Pheromones In Plethodontid Salamanders., Wilburn Beau Wilburn

Electronic Theses and Dissertations

Pheromones are an important type of chemical cue used by most animals to convey information between individuals. For more than 100 million years, male plethodontid salamanders have utilized a system of non-volatile, proteinaceous pheromones to regulate female mating behavior and receptivity. One of these pheromone components, Plethodontid Modulating Factor (PMF), is a hypervariable protein related to the three-finger protein (TFP) superfamily. Previous studies revealed that PMF persists as a rapidly evolving multi-isoform mixture. However, many characteristics of PMF as a pheromone remained undetermined, including gene structure and transcriptional regulation, translational regulation, protein structure, evolutionary mechanisms, and the isoform effects on …


Functional Implications Of Demyelination And The Molecular Control Of Remyelination In The Adult Mouse., Nicholas John Kuypers May 2014

Functional Implications Of Demyelination And The Molecular Control Of Remyelination In The Adult Mouse., Nicholas John Kuypers

Electronic Theses and Dissertations

Oligodendrocyte (OL) loss contributes to the functional deficits underlying diseases with a demyelinating component (Gajjar et al., 1997; Miller et al., 2002). Remyelination can restore these deficits (Duncan et al., 2009). Chapter 1 is an introduction to de- and re-myelination thus providing the necessary background information for consideration in subsequent chapters. Ethidium bromide (EB) has been extensively used in the rat and cat as a model of spinal cord demyelination. However, this lesion has not been addressed in the adult mouse. Therefore, Chapters 2 and 3 characterize a model of chronic EB-induced spinal cord demyelination in the mouse which can …


Invasive Plants As Drivers And Passengers Of Community Change In A Disturbed Urban Forest., Jeffery A. Masters May 2014

Invasive Plants As Drivers And Passengers Of Community Change In A Disturbed Urban Forest., Jeffery A. Masters

Electronic Theses and Dissertations

Invasive species can impact local ecosystems by decreasing biodiversity and local abundances of native species. Invasive species also frequently establish in disturbed habitats. An invasive species may dominate a habitat because the introduced species is a superior competitor (driver model) for resources or because the introduced species is more tolerant of noncompetitive processes such as anthropogenic disturbance that reduces the diversity and abundance of native species (passenger model). Ranunculus ficaria (Ranunculaceae) is an invasive plant species in the northeastern United States, and can be especially dense in urban riparian habitats. It emerges early and forms thick mats of vegetation that …


Epigenetic Modifications Associated With Aortic Remodeling In Hyperhomocysteinemia., Nithya Narayanan May 2014

Epigenetic Modifications Associated With Aortic Remodeling In Hyperhomocysteinemia., Nithya Narayanan

Electronic Theses and Dissertations

Background: Hyperhomocysteinemia (HHcy) is prevalent in hypertensive patients and is an independent risk factor for aortic pathologies. HHcy is known to cause an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) leading to accumulation of collagen in the aorta resulting in stiffness and development of hypertension. Although the exact mechanism of extracellular matrix remodeling (ECM) is unclear, emerging evidence implicates epigenetic regulation involving DNA methylation. The purpose of the study was to investigate whether inhibition of DNA methylation reduces high blood pressure by regulating aortic ECM remodeling in HHcy. Methods: In the first set of experiments, we …


Myocyte-Specific Overexpression Of Stromal Cell-Derived Factor 1 Facilitates Cardiac Regeneration And Improves Myocardial Function After Infarction In Mice., Detlef Ernst-Rudolf Obal May 2014

Myocyte-Specific Overexpression Of Stromal Cell-Derived Factor 1 Facilitates Cardiac Regeneration And Improves Myocardial Function After Infarction In Mice., Detlef Ernst-Rudolf Obal

Electronic Theses and Dissertations

Background: Interruption of cardiac stromal cell-derived factor 1 (SDF1)-CXCR4 axis by chronic AMD3100 administration increased myocardial injury after permanent coronary artery ligation, demonstrating the important role of this chemokine in cardiac regeneration. Hypothesis: Cardiomyocyte-specific conditional overexpression of SDF prevents heart failure after permanent coronary ligation and facilitates cardiac regeneration. Methods and Results: Tetracycline-controlled, a-myosine heavy chain promoter directed overexpression of cardiac SDF resulted in a significant increase of SDF expression (SDF: 8.1 ng / g protein) compared with littermate WT mice (0.02 ng / g protein) four weeks after doxycycline withdrawal. SDF overexpression increased AKT and casein kinase 1 levels …


Sa-4-1bbl As A Platform To Develop Adjuvant Systems For Prophylactic And Therapeutic Vaccines., Gunes Dinc 1984- May 2014

Sa-4-1bbl As A Platform To Develop Adjuvant Systems For Prophylactic And Therapeutic Vaccines., Gunes Dinc 1984-

Electronic Theses and Dissertations

Vaccines against infectious diseases are one of the most critical accomplishments in modern medicine. Despite significant progress in vaccinology, there is still a dire need for developing vaccines against various acute and chronic infections and cancer. In general, vaccines are categorized as prophylactic, given to healthy individuals to prevent disease, and therapeutic, administered to people who already have disease. As such, the nature, quality, and quantity of immune responses required for the efficacy of these two types vaccines are different. Prophylactic vaccines against infectious diseases primarily rely on the generation of neutralizing high titers of antibody for their efficacy. These …


The Anti-Obesogenic Effects Of Nitric Oxide., Brian Edward Sansbury 1985- May 2014

The Anti-Obesogenic Effects Of Nitric Oxide., Brian Edward Sansbury 1985-

Electronic Theses and Dissertations

Obesity is a strong risk factor for developing type 2 diabetes and cardiovascular disease and has quickly reached epidemic proportions with few tangible and safe treatment options. While it is generally accepted that the primary cause of obesity is energy imbalance, i.e., more calories are consumed than are utilized, understanding how caloric balance is regulated has proven a challenge. Molecular processes and pathways that directly regulate energy metabolism represent promising targets for therapy. In particular, nitric oxide (NO) is emerging as a central regulator of energy metabolism and body composition. NO bioavailability is decreased in animal models of obesity and …


Inflammation-Resolving Lipid Mediators Promote Revascularization To Enhance Wound Healing., Michael Jingyuan Zhang May 2014

Inflammation-Resolving Lipid Mediators Promote Revascularization To Enhance Wound Healing., Michael Jingyuan Zhang

Electronic Theses and Dissertations

Wound healing is a highly concerted cellular process that begins with inflammation and proceeds to resolution to revascularize the site of injury. Although inflammation is essential to revascularization during wound healing, it is now recognized that resolution is an active process that is equally important. Other investigations have implicated a beneficial effect of resolving inflammation and promoting resolution in the remission of inflammatory pathologies. Recently investigations have yielded a novel class of ?-3 fatty acid derived lipid mediators, biosynthesized by leukocytes, which are capable of resolving inflammation and promoting resolution. We therefore hypothesized that these leukocyte-derived pro-resolving lipid mediators can …


Regulation Of Macrophage Inflammatory Signaling Pathways By Amp-Activated Protein Kinase., Yanfang Zhu May 2014

Regulation Of Macrophage Inflammatory Signaling Pathways By Amp-Activated Protein Kinase., Yanfang Zhu

Electronic Theses and Dissertations

AMP-activated protein kinase, AMPK, is a conserved serine/threonine kinase with a critical function in the regulation of metabolic pathways in eukaryotic cells. Recently, AMPK has been shown to play an additional role as a regulator of inflammatory activity in leukocytes. Treatment of macrophages with chemical AMPK activators, or forced expression of a constitutively active form of AMPK, results in polarization to an antiinflammatory phenotype. Additionally, we reported previously that stimulation of macrophages with antiinflammatory cytokines such as IL-10, IL-4 and TGF-ß results in rapid activation of AMPK, suggesting that AMPK contributes to the suppressive function of these cytokines. In the …