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Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu Jan 2011

Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu

All ETDs from UAB

Changes in the glioma microenvironment including oxygen (O2) levels, supply of amino acid such as L-glutamate and L-cystine and glutathione (GSH) concentrations play a critical role in glioma biology. Previous data from our laboratory and others have implicated the L-cystine/L-glutamate exchanger, system xc- in the invasion and proliferation of cancers including glioma. The central aim of this dissertation was to characterize the contribution of L-cystine uptake, GSH synthesis and L-glutamate release to migration and proliferation of glioma cells. In my first study, I examined the role of system xc- mediated L-glutamate release on glioma migration. I show that activation of …

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Calcium Dynamics Of Glial Cells And Genetic Influences On Behavior Of The Nematode Caenorhabditis Elegans, Randy Franklin Stout Jan 2011

Calcium Dynamics Of Glial Cells And Genetic Influences On Behavior Of The Nematode Caenorhabditis Elegans, Randy Franklin Stout

All ETDs from UAB

A major challenge in neuroscience is understanding how the different neural cell types work together to process information and produce a behavioral output. Glial cells of the human brain have long been thought to act as support for the fundamental cell to cell communication at the core of cognition: neuronal synaptic communication. Research over the past several decades measuring glial activity and experimentally controlling glial cells in rodent model systems has shown that the two macroglia sub-types of glial cells (astrocytes and oligodendrocytes) have active roles in establishment, maintenance, and modulation of synaptic communication in the mammalian brain. Much of …

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Assessment Of Mitochondrial Stressors On Cellular Bioenergetics, Blake Reid Zelickson Jan 2011

Assessment Of Mitochondrial Stressors On Cellular Bioenergetics, Blake Reid Zelickson

All ETDs from UAB

The mitochondrion plays a central role in the maintenance of bioenergetic function through the production of ATP and essential metabolites. The development of mitochondrial bioenergetic defects is a hallmark of important pathologies such as cardiovascular and liver diseases. It is well established that a decrease in mitochondrial function, typically of 20-40%, is associated with the progression of these pathologies. Causal relationships have been more difficult to establish because of the challenge of assessing mitochondrial function in a cellular setting. Specifically, it is known that mitochondria function at less than their maximal respiratory capacity and the remainder, known as reserve or …

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Faculty Publications 2010, Lsu Health Sciences Center New Orleans Jan 2011

Faculty Publications 2010, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 844 publications.

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Hybrid Adult Neuron Culture Systems For Use In Pharmacological Testing, Darin Keay Edwards Jan 2011

Hybrid Adult Neuron Culture Systems For Use In Pharmacological Testing, Darin Keay Edwards

Electronic Theses and Dissertations

Neuronal culture systems have many applications, such as basic research into neuronal structure, function, and connectivity as well as research into diseases, conditions, and injuries affecting the brain and its components. In vitro dissociated neuronal systems have typically been derived from embryonic brain tissue, most commonly from the hippocampus of E18 rats. This practice has been motivated by difficulties in supporting regeneration, functional recovery and long-term survival of adult neurons in vitro. The overall focus of this dissertation research was to develop a dissociated neuronal culture system from human and animal adult brain tissue, one more functionally and developmentally correlative …

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Discovery And Optimization Of Novel Small-Molecular Inhibitors Suppressing Stat3-Dependent Tumor Process, Xiaolei Zhang Jan 2011

Discovery And Optimization Of Novel Small-Molecular Inhibitors Suppressing Stat3-Dependent Tumor Process, Xiaolei Zhang

Electronic Theses and Dissertations

With the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor, S3I-201, we have designed a diverse set of analogs. One of the most active analogs, S3I-201.1066 is derived to contain a cyclo-hexyl benzyl moiety on the amide nitrogen, which increases …

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Genetic And Physiological Contribution Of Adrenergic Cells In Heart Development, Kingsley Osuala Jan 2011

Genetic And Physiological Contribution Of Adrenergic Cells In Heart Development, Kingsley Osuala

Electronic Theses and Dissertations

The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are essential for cardiovascular development as embryos lacking NE/EPI begin to die abruptly between embryonic days 10.5 and 11.5 due to apparent cardiac failure. The objective of this research aims to elucidate the mechanism of the embryonic fatality observed in the NE/EPI deficient mouse model. Here we utilized the dopamine β- hydroxylase knockout (Dbh-/-) mouse model, which lacks the gene and subsequent enzyme necessary for the conversion of dopamine to norepinephrine. Embryonic mouse hearts were extracted from Dbh+/+ (control) and Dbh-/- (experimental model) mice for mRNA transcript expression profiling. These studies were …

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Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass Jan 2011

Genetically Modified Es Cells Enhance Cardiac Repair And Regeneration In The Infarcted Heart, Carley E. Glass

Electronic Theses and Dissertations

Transplanted embryonic stem (ES) cells following myocardial infarction (MI) contribute to limited cardiac repair and regeneration with improved function. Therefore novel strategies are still needed to enhance the efficacy by which ES cells differentiate into cardiac cell types and inhibit adverse remodeling in the infarcted myocardium. Our studies evaluate whether genetic manipulation of transplanted ES cells employing miR- 1, a pro-cardiac microRNA, and TIMP-1, an anti-apoptotic and anti-fibrotic protein, will enhance cardiac myocyte differentiation, inhibit native cardiac apoptosis, and reduce fibrosis in the infarcted myocardium. Furthermore, we assess levels of associated pro- (caspase-3, PTEN) and anti-(Akt) apoptotic proteins as well …

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Glial Differentiation Of Human Umbilical Stem Cells In 2d And 3d Environments, Hedvika Davis Jan 2011

Glial Differentiation Of Human Umbilical Stem Cells In 2d And 3d Environments, Hedvika Davis

Electronic Theses and Dissertations

During differentiation stem cells are exposed to a range of microenvironmental chemical and physical cues. In this study, human multipotent progenitor cells (hMLPCs) were differentiated from umbilical cord into oligodendrocytes and astrocytes. Chemical cues were represented by a novel defined differentiation medium containing the neurotransmitter norepinephrine (NE). In traditional 2 dimensional (2D) conditions, the hMLPCs differentiated into oligodendrocyte precursors, but did not progress further. However, in a constructed 3 dimensional (3D) environment, the hMLPCs differentiated into committed oligodendrocytes that expressed MBP. When co-cultured with rat embryonic hippocampal neurons (EHNs), hMLPCs developed in astrocytes or oligodendrocytes, based on presence of growth …

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The Effect Of High Dose Total Body Irradiation On Acth, Corticosterone, And Catecholamines In The Rat, Eric P. Cohen, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Hershel Raff Jan 2011

The Effect Of High Dose Total Body Irradiation On Acth, Corticosterone, And Catecholamines In The Rat, Eric P. Cohen, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Hershel Raff

Biomedical Sciences Faculty Research and Publications

Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic–pituitary–adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study …

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A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti Jan 2011

A Recombinant Myeloid-Binding Adenovirus For Targeted Pulmonary Gene Therapy, Michael O. Alberti

All ETDs from UAB

Inflammation and airway destruction are hallmarks of many debilitating lung diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), acute lung injury (ALI), and cancer. Gene-based therapeutic interventions that modulate this pathologic inflammatory response are likely to reduce the progressive destruction to lung airways. In this regard, a number of strategies have been evaluated for targeting the pul-monary vasculature; particularly those based on serotype 5 Adenovirus (Ad5). The ad-vantages of Ad over other vector systems include: in vivo stability, low oncogenic poten-tial, and large packaging capacity. Yet, specific and efficient gene delivery to the lung has been hampered …

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The Effect Of Sulfasalazine On Functional Recovery And Neuropathic Pain Following Spinal Cord Injury, Kelly Dunham Atkins Jan 2011

The Effect Of Sulfasalazine On Functional Recovery And Neuropathic Pain Following Spinal Cord Injury, Kelly Dunham Atkins

All ETDs from UAB

Spinal cord injury (SCI) is a devastating condition resulting in loss of motor function as well as sensory abnormalities. Insight into the pathophysiology of SCI progression has been gained through use of pre-clinical animal models, however these have not been successful in yielding pharmacological interventions for clinical management of SCI. One proposed reason for this discrepancy may be the use of SCI models which are not fully clinically relevant and do not assess the contribution of gray matter pathology to SCI functional outcomes. Post-SCI inflammation is well-documented and may lead to downstream loss of motor function. Additionally, inflammation is thought …

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Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley Jan 2011

Significance And Regulation Of Cd68 Expression In The Osteoclast, Jason Waid Ashley

All ETDs from UAB

The mucin-like Lysosome Associated Membrane Protein (LAMP) family member CD68 is a primarily myeloid lineage restricted transmembrane protein that is expressed in macrophages and osteoclasts. While the existence and expression pattern of human CD68 and mouse CD68 (sometimes called macrosialin) are well-known, and these molecules are routinely used as histological markers of tissue macrophages, the functional signific-ance of CD68 expression remains an unanswered question. Our overall goal is to deter-mine the significance and characterize the function of CD68 in osteoclasts and explore the effects of Receptor Activator of Nuclear Factor κB (RANK) signaling on CD68 post-translational modification. To achieve this …

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Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan Jan 2011

Role Of The Cardiomyocyte Circadian Clock In Modulating Myocardial Physiology And Pathophysiology, David Joseph Durgan

All ETDs from UAB

It is well established that multiple parameters of cardiovascular physiology and pathophysiology exhibit diurnal variations. For example, human heart rate and blood pressure peak during the morning and trough in the evening. Similarly, there is a morning prevalence for the onset of multiple adverse cardiovascular events, including myocardial ischemia, arrhythmias, and sudden cardiac death. Traditionally these rhythms have been attributed to rhythms in neurohumoral stimulation. However recent identification of the circadian clock mechanism in cardiovascular relevant cell types, including the cardiomyocyte, has prompted investigation into its role in modulating myocardial physiology and pathophysiology over the course of the day. Preliminary …

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The Role Of The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn Jan 2011

The Role Of The Classical Nf-Kb Pathway In Hsc Self-Renewal And Acute Myeloid Leukemia, Robert Jason Flynn

All ETDs from UAB

Acute myeloid leukemia (AML) comprises approximately 25% of newly diagnosed cases of leukemia each year. The constitutive activation of the classical NF-κB signaling pathway has been observed in up to 70% of AML cases, and could be due to mutations upstream involving the PI3K-Akt cascade, which is also constitutively active in a majority of cases. In mice, constitutive activation of Akt either through deletion of the negative regulator of PI3K-Akt, PTEN, or by expression of Myr-Akt induces rapid stem cell loss along with a lethal, transplantable myeloproliferative disorder and AML. These studies show that constitutive Akt and NF-κB signaling distinguish …

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The Study Of Intracellular Signaling Pathways In Schizophrenia, Adam Funk Jan 2011

The Study Of Intracellular Signaling Pathways In Schizophrenia, Adam Funk

All ETDs from UAB

INTRACELLULAR SIGNALING AND INTEGRATION ABNORMALITIES IN SCHIZOPHRENIA Adam J. Funk DEPARTMENT OF NEUROBIOLOGY ABSTRACT The pathophysiology of schizophrenia is complex and diverse, with many classes of receptors, neurotransmitters, and brain regions implicated in this illness. The many hypotheses proposed have yet to fully explain the heterogeneity of the genetic, postmor-tem, and clinical evidence. It is the goal of this dissertation to integrate the current hy-potheses of schizophrenia into a unified hypothesis of abnormal intracellular signaling and signal integration. Inconsistencies in genetic and postmortem findings suggest that the development of schizophrenia is multifaceted, and the heterogeneity of symptoms supports the hypothesis …

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Intracellular Distribution Of Glycogen Synthase Kinase-3beta In The Brain, Johanna C. Gandy Jan 2011

Intracellular Distribution Of Glycogen Synthase Kinase-3beta In The Brain, Johanna C. Gandy

All ETDs from UAB

The widely distributed serine/threonine kinase glycogen synthase kinase 3beta is well known for its multiple functions in the health brain tissue, which include cell fate, neuronal growth and remodeling, synaptic plasticity, and neuroinflammation. However much of GSK3beta focuses on its abnormal functions in neurological disorders like Alzheimer's Disease and psychiatric disorders. To maintain normal GSK3beta function in the brain, this constitutively active kinase must be strictly regulated. Many factors within the cell work together to influence GSK3beta activity. Two ways to regulate GSK3beta activity are through phosphorylation by upstream kinases or the formation of protein complexes that block substrate binding. …

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Human Cytomegalovirus Ul97 Kinase Activity Modifies Cell Cycle Checkpoint Regulators, Rachel Brooke Gill Jan 2011

Human Cytomegalovirus Ul97 Kinase Activity Modifies Cell Cycle Checkpoint Regulators, Rachel Brooke Gill

All ETDs from UAB

Human cytomegalovirus (CMV) infection results in destructive infections in neonates and immunocompromised individuals. Being the primary congenital infection in the United States, it can often result in permanent neurological deficits in infants. The current therapies for CMV infections all target the viral DNA polymerase and also have dose-limiting toxicities. Isolates resistant to ganciclovir (GCV), the therapy of choice, can sometimes overwhelm immunocompromised hosts. Better therapies for this infection are required. The CMV UL97 kinase is a key enzyme in the treatment of CMV infection because it phosphorylates GCV. Additionally, maribavir (MBV) specifically inhibits UL97 kinase activity and inhibits viral replication. …

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Oxidative Stress And Xanthine Oxidase In Acute And Chronic Cardiac Volume Overload In Rats, James Douglas Gladden Jan 2011

Oxidative Stress And Xanthine Oxidase In Acute And Chronic Cardiac Volume Overload In Rats, James Douglas Gladden

All ETDs from UAB

Mechanisms of left ventricular dysfunction in cardiac volume overload (VO) are not well understood and there is no medical therapy. Cardiac VO is marked by eccentric remodeling and contractile dysfunction ultimately resulting in cardiac failure. Oxidative stress is implicated in the pathophysiology of heart failure and recent evidence suggests xanthine oxidase (XO) plays a role in VO. To study VO, we used a rat model of aortocaval fistula (ACF). ACF results in early diastolic stress on the left ventricle (LV) and recapitulates the progressive nature of heart failure with contractile function being initially maintained and then depressed by 6 weeks. …

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Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Fetterman Jan 2011

Mitochondrial Genetics And Function In Cardiovascular Disease Susceptibility, Jessica L. Fetterman

All ETDs from UAB

While progress has been made in understanding the development and progression of cardiovascular disease (CVD), the mechanisms of CVD risk and initiation are not completely understood. It is widely accepted that CVD is the result of a combination of genetic and environmental factors but it is not known why some populations with otherwise similar risk factors appear more susceptible to CVD than others. It is also known that different strains of laboratory mice have distinct susceptibilities to CVD development. For example, C3H mice are resistant to diet induced atherogenesis whereas C57 animals are susceptible. We have also found that the …

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Pathophysiology Of Dyt1 Dystonia: Targeted Mouse Models, Chad Christopher Cheetham Jan 2011

Pathophysiology Of Dyt1 Dystonia: Targeted Mouse Models, Chad Christopher Cheetham

All ETDs from UAB

DYT1 dystonia is an inherited movement disorder caused by a trinucleotide deletion (DeltaGAG) in the DYT1 (TOR1A) gene, which codes for the torsinA protein. Dr. Yuqing Li's laboratory previously reported the characterization of a DYT1 dystonia mouse model, a knock-in carrying DeltaGAG in Dyt1 (KI), which displays a motor learning deficit of motor skill transfer. We report here that this motor learning deficit was reversed with an anticholinergic drug, trihexyphenidyl (THP), a drug commonly used to treat movement problems in dystonia patients. We further show a potential substrate for the pathophysiology, a reduction in D2 receptors in the striatum in …

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Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook Jan 2011

Analysis Of The Structural And Kinetic Properties Of Sult2a1 Induced By The Binding Of 3'-Phosphoadenosine-5'-Phosphosulfate, Ian Thomas Cook

All ETDs from UAB

Sulfation is an important Phase II drug metabolism reaction catalyzed by the cytosolic sulfotransferases (SULTs). SULT2A1 is a major SULT in liver and adrenal cortex that has been reported to sulfate a wide variety of substrates including bile acids, steroids, and drugs. The crystal structures of SULT2A1 suggest that PAPS binding causes a structural change. This study examines the kinetic changes in SULT2A1 caused by PAPS binding using computer modeling, enzyme kinetics, binding studies, and mammalian cells expressing SULT2A1. The data presented clearly demonstrate that the binding of PAPS changes the affinity of some substrates to SULT2A1 resulting in different …

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Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Jean Nick Jan 2011

Differential Contributions Of C-Kit Activating Mutations To Promotion Of Aml1-Eto Associated Neoplasia, Heidi Jean Nick

All ETDs from UAB

The t(8;21) translocation, which generates an AML1-ETO fusion protein (also known as RUNX1-ETO), is one of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML). Murine studies have demonstrated that AML1-ETO promotes the accumulation of myeloid progenitor cells with self-renewal capability and impaired differentiation capacity. However, AML1-ETO+ mice do not progress to AML in the absence of additional mutations, suggesting that expression of the translocation is insufficient for leukemogenesis. This hypothesis is supported by studies demonstrating the persistence of AML1-ETO-expressing hematopoietic progenitors obtained from patients in long-term clinical remission. Mutations affecting receptor tyrosine kinases, particularly c-KIT, are commonly detected …

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Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky Jan 2011

Sensitization Of Glioma To Death Receptor 5-Mediated Apoptosis Through Genotoxic Stress And Cell Cycle Disruption: A Study Of Mechanism, Michael L. Belenky

All ETDs from UAB

Our laboratory reported that a combination of ionizing radiation (IR) or temozolomide (Tmz), a DNA methylating agent clinically approved against glioblastoma multiforme (GBM), a type of human brain cancer, and TRA-8, an anti-DR5 monoclonal antibody produced synergistic cytotoxicity in GBM cells in culture and in mouse xenograft models through an yet unknown mechanism. I hypothesized that understanding of the synergy phenomenon can offer an insight into the nature of GBM vulnerability. The goals of this investigation were two-fold - to elucidate the mechanism of this enhancement in cytotoxicity, and to improve understanding of DR5 mediated apoptosis toward improvement of current …

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Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland Jan 2011

Exopolysaccharide: A Multi-Faceted Role In Mycoplasma Pulmonis, Jeffrey R. Bolland

All ETDs from UAB

The recently characterized exopolysaccharide of Mycoplasma pulmonis, EPS-I, has been identified as modulating the susceptibility to complement-mediated lysis and binding to host mucosal epithelium. M. pulmonis produces family of size- and phase-variable lipoproteins called Vsa. Previous evidence has strongly demonstrated that the length of the tandem repeat region of the M. pulmonis Vsa protein is associated with the susceptibility to the host innate immune system through complement-mediated lysis. Mycoplasmas producing a long form of Vsa, containing about 40 repeats, are resistant complement whereas strains that produce the short form of Vsa, 5 repeats or fewer, are susceptible. Furthermore, the size …

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The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist Jan 2011

The Role Of Protein Folding And Protein Trafficking In Human Disease, Cristy Davette Tower-Gilchrist

All ETDs from UAB

This dissertation documents my findings in two unrelated projects. Project 1: Expansion of CAG repeats encoding glutamine in huntingtin and ataxin 3 causes the neurodegenerative diseases Huntington's disease (HD) and spinocerebellar ataxia 3 (SCA3), respectively. Both poly-glutamine (polyQ) expanded proteins misfold and ag-gregate within the cell. Preventing aggregation of polyQ proteins through molecular or pharmacological approaches provide therapeutic advantage in animal models of HD and SCA3. I hypothesized that the UL97 kinase encoded by the human cytomegalovirus (HCMV) may be able to prevent the aggregation of polyQ proteins. Initially, I showed that the UL97 kinase prevents the deposition of aggregates …

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Low And High Let Irradiation Of Human Aortic Endothelial Cells Induces Dose And Time Dependent Adhesion Of Monocytes Which Is Mediated By Chemokines Expressed By The Irradiated Endothelium., Saman Fatima Khaled Jan 2011

Low And High Let Irradiation Of Human Aortic Endothelial Cells Induces Dose And Time Dependent Adhesion Of Monocytes Which Is Mediated By Chemokines Expressed By The Irradiated Endothelium., Saman Fatima Khaled

All ETDs from UAB

Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of xrays, iron (Fe56) ions, and protons on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X-rays, 0, 2, and 5 Gy Fe56 ions, and 0, 0.5, and 2 Gy protons followed by measurement of …

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The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz Jan 2011

The Role Of Trib3 In Insulin Resistance: Its Action As Nutrient Sensor And Regulator Of Insulin Action, Jiarong Lamiquiz

All ETDs from UAB

THE ROLE OF TRIB3 IN INSULIN RESISTANCE: ITS ACTION AS NUTRIENT SENSOR AND REGULATOR OF INSULIN ACTION JIARONG LIU LAMIQUIZ PATHOLOGY ABSTRACT Insulin resistance is a hallmark of Type 2 diabetes (T2DM). A reduced capacity for insulin to stimulate increases in glucose uptake and glucose oxidation in insulin sensitive tissues, such as skeletal muscle and adipose tissue, are common defects in patients with insulin resistance, T2DM, and other related diseases. Tribbles homolog 3 (TRIB3) has been demonstrated to play a role in insulin resistance by serving as a negative regulator of Akt in mouse liver, fat, and pancreas. In a …

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Erythropoiesis In The Absence Of Adult Hemoglobin, Shanrun Liu Jan 2011

Erythropoiesis In The Absence Of Adult Hemoglobin, Shanrun Liu

All ETDs from UAB

The mammalian erythrocyte is a highly specialized blood cell that differentiates via an orderly series of committed progenitors in the bone marrow in a process termed erythropoiesis. During erythroid development, hemoglobin synthesis increases from early erythroid progenitors to mature enucleated red blood cells (RBCs). Although hemoglobin is the most extensively studied protein in history, the role, if any, that hemoglobin plays in erythroid development remains obscure. In this study, I ask the question what happens during erythropoiesis in the absence of hemoglobin. I demonstrate that my original hypothesis that excess free heme would accumulate in the absence of globin chain …

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The Effects Of Simvastatin On Learning And Memory Mechanisms In Mice, Robert Mans Jan 2011

The Effects Of Simvastatin On Learning And Memory Mechanisms In Mice, Robert Mans

All ETDs from UAB

Statins, a widely prescribed class of cholesterol-lowering drug, inhibit HMG-CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. Due to the identification of cholesterol as a risk factor for developing Alzheimer's disease (AD), a number of studies have examined whether statins are neuroprotective against developing AD or dementia. While some epidemiological studies do indicate a lower prevalence of AD in people taking statins, other reports are contradictory. A consensus has therefore not been reached regarding the neuroprotective effects of statin treatment. Aside from the well-characterized reduction in circulating cholesterol resulting from statin therapy, numerous cholesterol-independent, pleiotropic effects have been …

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