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Full-Text Articles in Medicine and Health Sciences
Trp-Ing Down A Trk: A New Role For Transient Receptor Potential Channels As Novel Mediators Of Brain-Derived Neurotrophic Factor Actions At Both Sides Of The Excitatory Synapse, Michelle Dawn Amaral
Trp-Ing Down A Trk: A New Role For Transient Receptor Potential Channels As Novel Mediators Of Brain-Derived Neurotrophic Factor Actions At Both Sides Of The Excitatory Synapse, Michelle Dawn Amaral
All ETDs from UAB
Over the years, various roles for neurotrophins have been revealed, being initially described as survival signals for neurons making their initial synaptic contacts in the developing brain. Eventually, it was discovered that these molecules also play important modulatory roles in the adult brain. The work encompassed in this dissertation serves to characterize one particular neurotrophin, brain-derived neurotrophic factor (BDNF), which has been implicated in long-term potentiation (LTP), and its effects at CA3-CA1 synapses in the hippocampus following acute application in vitro. To this end, we have demonstrated the presence of a novel, non-selective cationic current that is initiated by BDNF …
Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini
Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini
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Novel combinatorial strategies need to be explored to achieve tumor eradication. In this regard, viral vector based gene therapy and nanotechnology offer unique possibilities for cancer therapy. As an example, multifunctional adenoviral (Ad) vectors capable of targeting, imaging, and successful cancer gene therapy have been advanced into multiple clinical trials. Similarly, novel multifunctional gold nanoparticles (AuNPs) have been utilized for drug delivery, targeting, imaging, and hyperthermia tumor therapy. Therefore, to accrue the benefits of both gene therapy and nanotechnology for cancer therapy, we proposed to combine Ad vectors and AuNPs in a single multifunctional nanodevice. Towards this goal, herein, we …
A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody V
A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody V
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Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anti-cancer agents designed to infect and lyse tumor cells. For increased efficacy, CRAds have been armed with therapeutic transgenes. Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, represents a promising candidate with which to arm a CRAd intended to treat osteolytic bone metastases. We hypothesize that a CRAd armed with OPG will inhibit breast cancer bone metastasis and reduce tumor burden in the bone by directly lysing tumor cells and by …
Microbial Biofilm Attachment To Caenorhabditis Elegans, Kevin Drace
Microbial Biofilm Attachment To Caenorhabditis Elegans, Kevin Drace
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The closely related bacterial species Xenorhabdus nematophila, Yersinia pestis and Y. pseudotuberculosis make biofilms capable of adhering to the head of the model nematode Caenorhabditis elegans. Y. pestis uses biofilms to block the digestive tract of its vector, the flea, in order to enhance its efficiency of transmission. I investigated the role of biofilms in X. nematophila and found that, like its Yersinia sp. counterparts, production of biofilm requires a four-gene operon: hmsHFRS. X. nematophila is an insect pathogen and an obligate symbiont of the nematode Steinernema carpocapsae. However, an X. nematophila hmsH mutant that failed to make biofilms on …
Calmodulin Binding To Cellular Flice Like Inhibitory Protein Modulates Fas-Induced Signaling And Tumorigenesis In Cholangiocarcinoma, Pritish Subhash Pawar
Calmodulin Binding To Cellular Flice Like Inhibitory Protein Modulates Fas-Induced Signaling And Tumorigenesis In Cholangiocarcinoma, Pritish Subhash Pawar
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Cholangiocarcinoma, a fatal tumor arising from biliary epithelium, has very poor 5-year survival rate due to lack of early diagnosis and effective therapies. Induction of the Fas-mediated apoptosis is a promising therapeutic target in this tumor. Studies from our group and others have indicated that Fas-expression correlates inversely with disease progression and that CaM-antagonists induce apoptosis in cholangiocarcinoma cells in a Fas related manner. Further, we reported a direct and dynamic interaction of CaM and Fas and that CaM is recruited into the Fas-stimulated death inducing signaling complex (DISC), suggesting a cross talk between Fas and CaM pathways. The studies …
Growth Hormone Signaling And Action In Osteoblasts, Douglas J. Digirolamo
Growth Hormone Signaling And Action In Osteoblasts, Douglas J. Digirolamo
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Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exert profound growth promoting actions during pre- and post-natal skeletal development. GH and IGF- 1 appear to cause these anabolic actions by influencing a variety of effects on osteoblast proliferation, differentiation, and survival. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including bone, the individual contributions of these two molecules to anabolic responses in bone remains poorly defined. In this dissertation research, I sought to distinguish the direct and indirect (IGF-1 dependent) GH actions on osteoblasts. In the first section of this thesis, I …
Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett
Characterization Of Sortase And Its Effect On The Virulence Of Streptococcus Pneumoniae, Allison E. Bennett
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Sortases are transpeptidases that covalently link surface proteins to the stempeptide on the cell wall peptidoglycan of Gram-positive bacteria. This work endeavored to characterize the various sortase enzymes and their effect on the virulence of Streptococcus pneumoniae. The genome of S. pneumoniae may encode up to four sortase enzymes. We found that 38 of 54 strains of serotype 6B clonal complex 14 (CC14) carry the genes for the secondary sortases srtB, srtC, and srtD. The presence of these sortases did not seem to influence the ability of strains within CC14 to infect the nasopharynx, lungs, or blood of strains within …
The Developmental Functions Of Bdnf And Mecp2 On Dendritic And Synaptic Structure, Christopher A. Chapleau
The Developmental Functions Of Bdnf And Mecp2 On Dendritic And Synaptic Structure, Christopher A. Chapleau
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Mutations in the transcriptional repressor MeCP2 cause Rett Syndrome (RTT), a mental retardation disease associated with reduced dendritic architecture of cortical pyramidal neurons, in addition to a decrease in the number of dendritic spines. I present the first quantification analysis of spine density in postmortem human brain tissue, demonstrating that hippocampal CA1 pyramidal neurons have reduced spine densities in RTT patients throughout their lives. One gene that MeCP2 regulates is BDNF, an important developmental factor that modulates synaptic transmission and plasticity, as well as spine formation and maturation. In immature cultured hippocampal neurons, cell-autonomous expression of BDNF accelerates the differentiation …
Analysis Of The Role Of Fcrl5 And Figlers In B Cell Development, Signaling, And Malignancy, Christopher L. Haga
Analysis Of The Role Of Fcrl5 And Figlers In B Cell Development, Signaling, And Malignancy, Christopher L. Haga
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The regulation of signaling and migration is critical to B lymphocyte development, activation, and proliferation. This dissertation reports a functional role for Fc receptor-like molecule 5 (FCRL5), a B cell specific member of the Fc receptor-like family of molecules, and the discovery of a novel family of conserved transmembrane proteins with fibronectin, immunoglobulin, and leucine-rich repeat domains (FIGLER) expressed in bone marrow and B lineage cells. Until now, the signaling potential of FCRL5 was unknown. A panel of FcRIIB/FCRL5 chimeric receptors were created and expressed in a B cell line lacking endogenous FcRIIB. Coligation of the chimeric receptor with the …
Role Of The Gm/Gn Glycoprotein Complex In The Final Assembly And Egress Of The Human Cytomegalovirus (Hcmv), Magdalena Anna Krzyzaniak
Role Of The Gm/Gn Glycoprotein Complex In The Final Assembly And Egress Of The Human Cytomegalovirus (Hcmv), Magdalena Anna Krzyzaniak
All ETDs from UAB
HCMV consists of a dsDNA genome enclosed by, an icosahedral capsid surrounded by a layer of tegument proteins; the virion structure is enclosed in a lipid envelope rich in virus expressed glycoproteins. The HCMV envelope contains an incompletely defined number of glycoproteins. The glycoprotein M (gM) and glycoprotein N (gN) form a gM/gN protein complex which is the most abundant protein component of the HCMV envelope. Recent studies have indicated that deletion of the viral gene encoding either gM or gN is lethal for HCMV. The gM C-terminal cytoplasmic tail (gM-CT) revealed an acidic cluster and a tyrosine-based trafficking motifs. …
Mechanism Of Interferon-Beta-Mediated Inhibition Of Il-8 Gene Expression, Travis Laver
Mechanism Of Interferon-Beta-Mediated Inhibition Of Il-8 Gene Expression, Travis Laver
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Interleukin-8 (IL-8) is a potent chemoattractant of numerous cells, particularly neutrophils, in the innate immune response. In addition to immune functions, IL-8 is known to contribute to the pathogenesis of a number of diseases, including cancer. Interferon-β (IFN-β), a Type I interferon, inhibits the expression of IL-8, but the details of this effect are not known. In this study we investigate transcriptional control of the IL- 8 gene and the mechanism by which IFN-β exerts inhibitory effects on IL-8. Herein we show that stimulation of U87-MG glioma cells with phorbol 12-myristate 13-acetate (PMA) results in a rapid recruitment of NF-κB …
The Au-Rich Element Mrna Decay-Promoting Activity Of Brf1 Is Regulated By Mitogen-Activated Protein Kinase Activated Protein Kinase 2, Sushmit Maitra
The Au-Rich Element Mrna Decay-Promoting Activity Of Brf1 Is Regulated By Mitogen-Activated Protein Kinase Activated Protein Kinase 2, Sushmit Maitra
All ETDs from UAB
Regulated mRNA decay is a highly important process for the tight control of gene expression. Inherently unstable mRNAs contain AU-rich elements (AREs) in the 3’ untranslated regions that direct rapid mRNA decay by interaction with decay-promoting ARE-binding proteins (ARE-BPs). The decay of ARE-containing mRNAs is regulated by signaling pathways, which are believed to directly target ARE-BPs. Here, we show that BRF1 involved in ARE-mediated mRNA decay (AMD) is phosphorylated by MAPK-activated protein kinase 2, MK2. In vitro kinase assays using different BRF1 fragments suggest that MK2 phosphorylates BRF1 at four distinct sites, S54, S92, S203, and an unidentified site at …
Modulation Of Transforming Growth Factor (Tgf)-Ss1 And Its Implications In Breast Cancer Metastasis, Lakisha Dionne Moore
Modulation Of Transforming Growth Factor (Tgf)-Ss1 And Its Implications In Breast Cancer Metastasis, Lakisha Dionne Moore
All ETDs from UAB
Overexpresssion of transforming growth factor (TGF)-β has been implicated in promoting immune suppression, tumor angiogenesis, tumor cell migration, and invasion in many cancers including carcinoma of the breast. Thus, targeted downregulation of TGF-β1 expression in breast cancer in situ and determination of its implications potentially could provide new treatment approaches for disease management. siRNA constructs targeting TGF-β1 were validated and used to develop clonal derivatives of the MDA-MB-435 metastatic breast cancer cell line. Inhibition of TGF-β1 expression in MDA-MB-435 cells showed decrease in migration and invasion in vitro with an increase in proliferation. In vivo analysis indicated a 90% decrease …
The Role Of Centaurin Alpha-1 In The Regulation Of Neuron Al Differentiation, Carlene Drucilla Moore
The Role Of Centaurin Alpha-1 In The Regulation Of Neuron Al Differentiation, Carlene Drucilla Moore
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In the nervous system, PI 3-kinase has been implicated in neuronal differentiation. My studies have focused on a candidate neuronal PI 3-kinase target centaurin alpha-1, which binds PtdIns(3,4,5)P3, and is an Arf6 GAP. Centaurin alpha-1 is localized in dendrites, dendritic spines and synapses, and is required for neuronal differentiation and spine morphogenesis. In dissociated neuronal cultures, expression of centaurin alpha-1 enhances dendritic branching, and increases dendritic filopodia, lamellipodia and spine-like protrusions. Expression of centaurin alpha-1 GAP inactive mutant or knocking down centaurin alpha-1 levels using siRNA leads to inhibition of dendritic outgrowth and branching. Manipulations of centaurin alpha-1 also disrupt …
Investigation Of Lipoteichoic Acid Structure And Function To Establish Its Role In Gram-Positive Bacterial Infections, Ho Seong Seo
Investigation Of Lipoteichoic Acid Structure And Function To Establish Its Role In Gram-Positive Bacterial Infections, Ho Seong Seo
All ETDs from UAB
Lipoteichoic acid (LTA) is an essential bacterial membrane polysaccharide (cell wall component) that is linked to a glycerol backbone with two acyl chains. Since an antibody to LTA has been shown to protect from Gr+ bacterial infections or colonization, and the mutant Gr+ bacteria which produce less amount of LTA have less pathogenic than WT, LTA may be an important role in Gr+ bacterial infection and inflammation. The currently accepted structure of pneumococcal LTA has the pentameric repeating unit bound to the lipid anchor {Glc(β1��3)AATGal(β1��3)Glc(α1��3)-acyl2Gro}. Unlike the lipid anchor of other Gr+ bacterial LTA, this pneumococcal LTA lipid anchor has …
Analysis Of The Hedgehog Pathway In Pancreatic Adenocarcinoma, Adam Steg
Analysis Of The Hedgehog Pathway In Pancreatic Adenocarcinoma, Adam Steg
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Pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer mortality in the United States. Despite the use of highly aggressive treatment regimens (surgery, chemotherapy and radiation), almost all patients succumb to metastatic disease within 6-10 months of diagnosis. The hedgehog (HH) signaling pathway was originally discov-ered to play a critical role in mammalian embryological development. Interestingly, re-cent studies have suggested that aberrant expression of this pathway is involved in the initiation and continued growth of PAC. Small molecules that antagonize the transmem-brane protein Smoothened (Smo), a critical signaling component of the HH pathway, have proven effective in decreasing PAC …
Mapks Regulate Nuclear Import Of Human Papillomavirus Type 11 Replicative Helicase E1, Jei-Hwa Yu
Mapks Regulate Nuclear Import Of Human Papillomavirus Type 11 Replicative Helicase E1, Jei-Hwa Yu
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Papillomaviruses (PV) are prevalent pathogens that infect human or animal squamous epithelia. Its genome is a double strand circular DNA of approximately 7.9 kb. It contains origin of replication (ori) and encodes early viral proteins for viral DNA amplication, and late capsid proteins for packaging viron. The viral DNA replicates as extrachromosomal nuclear plasmid in the host cell. Infections by low risk virus, such as HPV-6 and -11, can result in benign papillomas, condylomata, and low grade squamous intraepithelial dysplasias (SIL), whereas infection by high risk virus, such as HPV-16 and -18, can progress to high grade SIL, carcinoma in …
Human Papillomavirus: Segregation And Replication, Luan D. Dao
Human Papillomavirus: Segregation And Replication, Luan D. Dao
All ETDs from UAB
Human papillomavirus are small DNA tumor viruses. The viral genome is a small circular double stranded DNA that replicates autonomously as an extrachromosomal plasmid. Occasionally infections by the high risk HPV viruses can lead to DNA integration and progression to cancer. How the HPV DNA is maintained and becomes established in the dividing host cells is not well understood. Additionally, as a double-stranded DNA virus it is likely that double-stranded DNA breaks in the viral genome, either from replication or random damage, will trigger a DNA repair response from the host cell. Such responses have been alternatively reported to be …
Thrombospondin Type-1 Repeats And Their Potential Role In Inhibiting Glioblastoma Angiogenesis, Joshua C. Anderson
Thrombospondin Type-1 Repeats And Their Potential Role In Inhibiting Glioblastoma Angiogenesis, Joshua C. Anderson
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Thrombospondin-1 (TSP-1) is a 420 kilodalton homotrimeric protein; it is one of the first identified anti-angiogenic proteins found to be expressed in some normal tissues. Peptides derived from the type-1 repeat (TSR) domains of full length TSP-1 have been shown to have anti-angiogenic activity, and thus anti-tumor activity in some non-glioma tumor models. I hypothesized that peptides derived from the TSRs of TSP-1, such as ABT-510, could inhibit angiogenesis and thus malignant glioma tumor growth in vivo. I found that ABT-510 inhibited angiogenesis of the human brain microvascular endothelial cell (MvEC) in an in vitro tubulomorphogenesis assay. To determine the …
Metabolism Of Neutrophil-Deprived Chlorinated Isoflavones, Tracy Lyn D'Alessandro
Metabolism Of Neutrophil-Deprived Chlorinated Isoflavones, Tracy Lyn D'Alessandro
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Despite medical advances in both drug therapy and surgical techniques, Americans mostly die from heart disease. Many belong to the low- and middle-class families who do not have sufficient access to medical care due to its high costs. An alternative is the development of healthier lifestyles such as diet which may play a positive role in chronic disease management. Epidemiological and migratory studies suggest that soy plays a pivotal role in the decreased incidence of heart disease in East Asian countries, such as China, Japan, and Korea. The role of soy in cardiovascular disease progression has been the subject of …
Analysis Of Hiv-1 Variable Loop 3-Specific Neutralizing Antibody Responses By Hiv-2/Hiv-1 Envelope Chimeras, Katie L. Davis
Analysis Of Hiv-1 Variable Loop 3-Specific Neutralizing Antibody Responses By Hiv-2/Hiv-1 Envelope Chimeras, Katie L. Davis
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Defining the epitope specificities of the neutralizing antibody response to the HIV-1 envelope protein (Env) during natural human infection and in response to vaccination by HIV-1 immunogens could provide insight into the mechanisms of virus immune containment and facilitate vaccine design. Transplantation of discrete HIV-1 neutralizing epitopes into HIV-2 Env scaffolds may provide a sensitive, biologically functional context in which to quantify specific antibody reactivities in complex sera. Here we describe the development of a novel HIV-2 proviral scaffold (pHIV-2KR.X7) into which we have substituted the env V3 region of several laboratory and primary HIV-1 strains to yield a panel …
Functionalizing Hydroxyapatite Biomaterials With Biomimetic Peptides Of Integrin Ligands, Kristin Marie Hennessy
Functionalizing Hydroxyapatite Biomaterials With Biomimetic Peptides Of Integrin Ligands, Kristin Marie Hennessy
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Hydroxyapatite (HA) coatings of hard tissue implants have been shown to increase osseointegration, but the mechanisms by which HA improves implant integration are not well understood. Numerous studies have shown that modifying HA with adhesive peptides, including RGD, and the collagen I mimetics, DGEA and P15, stimulates the adhesion of mesenchymal stem cells (MSCs), a cell type that differentiates along the osteoblast lineage. However, HA is a highly adsorptive biomaterial, and therefore it is unlikely that cells at the implant site would ever encounter a peptidemodified HA surface in the absence of an adsorbed protein layer. In fact, our laboratory …
Using Rna Interference To Study The Function Of The Tethering Protein P115 In Er-Golgi Traffic, Robert Grabski
Using Rna Interference To Study The Function Of The Tethering Protein P115 In Er-Golgi Traffic, Robert Grabski
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Metazoan cells are characterized with elaborate network of intracellular membranous compartments. These membranes allow the cell to spatially separate antagonistic processes and environments, and maintain sequential order of reactions necessary for maturation and secretion of biosynthetic cargo. The core transport machinery consists of coat proteins, tethering factors, SNAREs and small Ras-like GTPases. We have explored the function of the tethering factor p115 in organellogenesis and in secretory traffic. The p115-depleted system was utilized to explore structurefunction relationships within p115. Here, we analyzed the architecture of the Golgi after RNAi induced depletion of p115. We show that in p115 depleted cells …
Effects Of Aerobic Exercise On The Asthmatic Lung, Matthew M. Hewitt
Effects Of Aerobic Exercise On The Asthmatic Lung, Matthew M. Hewitt
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Asthma is identified by the clinical symptoms of wheezing, chest tightness, dyspnea and cough, and by the presence of airway hyperresponsiveness (AHR) to inhaled stimuli. We have reported previously that repeated bouts of moderate intensity aerobic exercise attenuate airway inflammatory responses in a mouse model of atopic asthma. Because the effects of exercise on physiological responses are dependent upon several variables, including total exercise duration, the hypothesis of the current work was that differing amounts of moderate intensity aerobic exercise exert dissimilar effects on AHR and airway inflammation. The aims to test this hypothesis included: 1) determine the effect of …
Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee
Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee
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Retinol dehydrogenase 12 (RDH12) is a member of the microsomal short-chain dehydrogenase/reductase superfamily of proteins that is highly expressed in photorecep-tor cells. Mutations in RDH12 are associated with severe early-onset autosomal recessive retinal dystrophy, leading to legal blindness. Disease-associated RDH12 variants exhibit lower protein levels when expressed in eukaryotic cells. However, the physiological role of RDH12 remains unclear. As established previously, RDH12 recognizes both retinoids and lipid peroxidation products (medium-chain aldehydes) as substrates and exhibits the highest catalytic efficiency for all-trans-retinaldehyde. As the main goal of this dissertation, we characterized the catalytic properties of RDH12 and its naturally occurring mutants …
Mechanism Of The Cross Talk Between Growth Hormone Receptor And Epidermal Growth Factor Receptor, Xin Li
Mechanism Of The Cross Talk Between Growth Hormone Receptor And Epidermal Growth Factor Receptor, Xin Li
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EGF receptor (EGFR) is a receptor tyrosine kinase, mediating cell growth from ectodermal and mesodermal origin. The overexpression and aberrant function of EGFR are involved in a wide range of human carcinomas. Growth hormone receptor (GHR) coexists with EGFR in various cell types and implicated in malignant tumor behavior. Previously in our lab, we found that via ERK activation GH can threonine phosphorylate EGFR and reduce EGF-induced EGFR downregulation. GH also synergizes with EGF in activating ERK. In this project, using reconstitution, we studied the mutation of the ERK phosphorylation consensus residue on EGFR, 669T. CHO-GHR cells, which lack EGFR …
Molecular Regulation Of Pax5-Mediated Biological Functions, Ti He
Molecular Regulation Of Pax5-Mediated Biological Functions, Ti He
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B lineage cells are major players in the adaptive immune system. Pax5 is essential for B lineage cell development and function. Pax5 controls B lineage cell developmental progression by regulating expression of many B lineage specific genes and the B lineage specific VH to DJH recombination; and the meantime, Pax5 also represses the transcription of lineage- and developmental stage- inappropriate genes to restrict the B lineage developmental pathway. It is not clear how Pax5-mediated function can be regulated to fulfill its role in different biological reactions. In this dissertation, we focused on the study of the molecular regulation of Pax5-mediated …
Biogenesis, Trafficing, And Function Of Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator (Cftr), Asta Jurkuvenaite
Biogenesis, Trafficing, And Function Of Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator (Cftr), Asta Jurkuvenaite
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Cystic fibrosis (CF) is a genetic disease resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel that functions at the apical surface of epithelial cells and plays a critical role in mucociliary clearance. The most common mutation in the CFTR gene involves a deletion of phenylalanine at position 508 in the protein (ΔF508 CFTR). ΔF508 CFTR is recognized as misfolded in the endoplasmic reticulum (ER) and is degraded. In vitro manipulations such as culturing cells at 27°C can “rescue” ΔF508 CFTR to the plasma membrane (rΔF508 CFTR), but no pharmacological agent has produced comparable …
Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton
Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton
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seeking behavior following chronic drug use lasts for many months or even years. Short-term withdrawal experiments have suggested that the neuroadaptations thought to underlie learning and memory may also contribute to addictive behavior. However, there is little information about the physiological mechanisms that participate in craving and relapse following long-term withdrawal. Here I show in hippocampal slices from rats treated with nicotine for 1 week that there is a change in the excitability of CA1 pyramidal cells that persists for up to 9 months following the cessation of drug treatment. The expression of this enhanced excitability is dependent on different …
Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams
Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams
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Insulin secretory defects within pancreatic beta-cells (β-cells) of islets of Langerhans play a role in the pathogenesis of diabetes mellitus. Furthermore, it is also well established that ATP and zinc are co-secreted with insulin in response to elevated extracellular glucose. Despite this knowledge, the physiological roles of extracellular secreted ATP and zinc within islets are ill-defined. We hypothesized that secreted ATP and zinc are autocrine purinergic signaling molecules that activate P2X purinergic receptor (P2XR) channels expressed by β-cells to enhance glucose-stimulated insulin secretion (GSIS). To test this postulate, ELISA, luciferin/luciferase-based bioluminescence and zinquin-based fluorescence assays were utilized to examine insulin, …