gp120-induced alterations of human astrocyte function: Na+/H+exchange, K+conductance, and glutamate flux

2000 ◽  
Vol 279 (3) ◽  
pp. C700-C708 ◽  
Author(s):  
Holly K. Patton ◽  
Zhen-Hong Zhou ◽  
James K. Bubien ◽  
Etty N. Benveniste ◽  
Dale J. Benos
Keyword(s):  
Glutamate Uptake ◽  
Cell Types ◽  
Neurological Complications ◽  
Ph Sensitive ◽  
Human Astrocyte ◽  
Physiological Processes ◽  
Human Astrocytes ◽  
Rat Astrocytes ◽  
Immunodeficiency Syndrome ◽  
Intracellular Alkalinization

Many human immunodeficiency virus (HIV)-infected patients suffer from impaired neurological function and dementia. This facet of the disease has been termed acquired immunodeficiency syndrome (AIDS)-associated dementia complex (ADC). Several cell types, including astrocytes and neurons, are not productively infected by virus but are involved in ADC pathophysiology. Previous studies of rat astrocytes showed that an HIV coat protein (gp120) accelerated astrocyte Na+/H+exchange and that the resultant intracellular alkalinization activated a pH-sensitive K+conductance. The present experiments were conducted to determine whether gp120 affected human astrocytes in the same fashion. It was found that primary human astrocytes express a pH-sensitive K+conductance that was activated on intracellular alkalinization. Also, gp120 treatment of whole cell clamped human astrocytes activated this conductance specifically. Furthermore, gp120 inhibited glutamate uptake by primary human astrocytes. These altered physiological processes could contribute to pathophysiological changes in HIV-infected brains. Because the gp120-induced cell physiological changes were partially inhibited by dimethylamiloride (an inhibitor of Na+/H+exchange), our findings suggest that modification of human astrocyte Na+/H+exchange activity may provide a means of addressing some of the neurological complications of HIV infection.

scholarly journals Syndecans and Pancreatic Ductal Adenocarcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Physiological Processes ◽  
Extracellular Matrix Components ◽  
Detection And Diagnosis ◽  
And Migration ◽  
Early Detection And Diagnosis

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.

scholarly journals Isoflurane Regulates Proliferation, Apoptosis, and Inflammatory Response of Lipopolysaccharide-Induced Human Astrocyte through the miR-206/BDNF Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jianying Wang ◽  
Zhiyuan Liu ◽  
Xue Wang ◽  
Yu Liu
Keyword(s):  
Inflammatory Response ◽  
Western Blotting ◽  
Annexin V ◽  
Luciferase Reporter ◽  
Bdnf Expression ◽  
Human Astrocyte ◽  
Human Astrocytes ◽  
Proliferation And Apoptosis ◽  
Proliferation Activity ◽  
Normal Human

Objective. To investigate the effect of isoflurane (ISO) on the proliferation, apoptosis, and inflammatory response of lipopolysaccharide- (LPS-) induced normal human astrocytes (NHAs) by regulating the miR-206/BDNF axis. Methods. NHA proliferation activity was measured by MTT; NHA apoptotic rates were measured by Annexin V-FITC/PI; western blotting was used to measure the BDNF expression; ELISA was used to measure the IL-6, IL-1β, and TNF-α expression in NHAs; qPCR was used to measure the expressions of miRNAs that are related to NHAs proliferation and apoptosis; dual-luciferase reporter was constructed to validate the targeting relationship between miR-206 and BDNF. Results. LPS increased the proliferation activity and decreased the apoptosis rate of NHAs which were effectively reversed by the ISO (p<0.05); LPS significantly inhibited the expression of miRNAs related to proliferation and apoptosis in NHAs (p<0.05, p<0.01), whereas ISO significantly increased the expression of miR-206 (p<0.01) by downregulating the expression of BDNF, thus inhibiting NHA proliferation and inflammatory response and enhancing apoptosis. Conclusion. ISO can inhibit the expression of BDNF by upregulating the expression of miR-206, thereby inhibiting the proliferation and inflammatory response of NHAs and promoting its apoptosis.

scholarly journals Implications of hematopoietic stem cells heterogeneity for gene therapies

Gene Therapy ◽  
2021 ◽  
Author(s):  
Jeremy Epah ◽  
Richard Schäfer
Keyword(s):  
Immune Cell ◽  
Ex Vivo ◽  
Bone Marrow Failure ◽  
Cell Types ◽  
Blood Disorders ◽  
Hematopoietic Stem ◽  
Therapeutic Concept ◽  
Gene Therapies ◽  
Bone Marrow Failure Syndromes ◽  
Immunodeficiency Syndrome

AbstractHematopoietic stem cell transplantation (HSCT) is the therapeutic concept to cure the blood/immune system of patients suffering from malignancies, immunodeficiencies, red blood cell disorders, and inherited bone marrow failure syndromes. Yet, allogeneic HSCT bear considerable risks for the patient such as non-engraftment, or graft-versus host disease. Transplanting gene modified autologous HSCs is a promising approach not only for inherited blood/immune cell diseases, but also for the acquired immunodeficiency syndrome. However, there is emerging evidence for substantial heterogeneity of HSCs in situ as well as ex vivo that is also observed after HSCT. Thus, HSC gene modification concepts are suggested to consider that different blood disorders affect specific hematopoietic cell types. We will discuss the relevance of HSC heterogeneity for the development and manufacture of gene therapies and in exemplary diseases with a specific emphasis on the key target HSC types myeloid-biased, lymphoid-biased, and balanced HSCs.

Generation of Slow Network Oscillations in the Developing Rat Hippocampus After Blockade of Glutamate Uptake

2007 ◽  
Vol 98 (4) ◽  
pp. 2324-2336 ◽  
Author(s):  
Adriano Augusto Cattani ◽  
Valérie Delphine Bonfardin ◽  
Alfonso Represa ◽  
Yehezkel Ben-Ari ◽  
Laurent Aniksztejn
Keyword(s):  
Nmda Receptors ◽  
Glutamate Uptake ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Proper Function ◽  
Network Oscillations ◽  
Bath Application ◽  
Hippocampal Network

Cell-surface glutamate transporters are essential for the proper function of early cortical networks because their dysfunction induces seizures in the newborn rat in vivo. We have now analyzed the consequences of their inhibition by dl-TBOA on the activity of the developing CA1 rat hippocampal network in vitro. dl-TBOA generated a pattern of recurrent depolarization with an onset and decay of several seconds' duration in interneurons and pyramidal cells. These slow network oscillations (SNOs) were mostly mediated by γ-aminobutyric acid (GABA) in pyramidal cells and by GABA and N-methyl-d-aspartate (NMDA) receptors in interneurons. However, in both cell types SNOs were blocked by NMDA receptor antagonists, suggesting that their generation requires a glutamatergic drive. Moreover, in interneurons, SNOs were still generated after the blockade of NMDA-mediated synaptic currents with MK-801, suggesting that SNOs are expressed by the activation of extrasynaptic NMDA receptors. Long-lasting bath application of glutamate or NMDA failed to induce SNOs, indicating that they are generated by periodic but not sustained activation of NMDA receptors. In addition, SNOs were observed in interneurons recorded in slices with or without the strata pyramidale and oriens, suggesting that the glutamatergic drive may originate from the radiatum and pyramidale strata. We propose that in the absence of an efficient transport of glutamate, the transmitter diffuses in the extracellular space to activate extrasynaptic NMDA receptors preferentially present on interneurons that in turn activate other interneurons and pyramidal cells. This periodic neuronal coactivation may contribute to the generation of seizures when glutamate transport dysfunction is present.

Compartmentalization of GPCR signalling controls unique cellular responses

2016 ◽  
Vol 44 (2) ◽  
pp. 562-567 ◽  
Author(s):  
Andrew M. Ellisdon ◽  
Michelle L. Halls
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Attrition Rates ◽  
Physiological Processes ◽  
Simple Chain ◽  
G Protein Coupled ◽  
Major Drug ◽  
Very High

With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs.

scholarly journals Astroglial FMRP modulates synaptic signaling and behavior phenotypes in FXS mouse model

2020 ◽  
Author(s):  
Shan-Xue Jin ◽  
Haruki Higashimori ◽  
Christina Schin ◽  
Alessandra Tamashiro ◽  
Yuqin Men ◽  
...  
Keyword(s):  
Glutamate Uptake ◽  
Fragile X ◽  
Cell Types ◽  
Skill Learning ◽  
Spine Density ◽  
Novelty Preference ◽  
Synaptic Signaling ◽  
Selective Loss ◽  
State Duration ◽  
Cortical Hyperexcitability

AbstractFragile X syndrome (FXS) is one of the most common inherited intellectual disability (ID) disorders, in which the loss of FMRP protein induces a range of cellular signaling changes primarily through excess protein synthesis. Although neuron-centered molecular and cellular events underlying FXS have been characterized, how different CNS cell types are involved in typical FXS synaptic signaling changes and behavioral phenotypes is largely unknown. Recent evidence suggests that selective loss of astroglial FMRP is able to dysregulate glutamate uptake, increase spine density, and impair motor-skill learning. Here we investigated the effect of astroglial FMRP on synaptic signaling and FXS-related behavioral and learning phenotypes in astroglial Fmr1 cKO and cON mice in which FMRP expression is selectively diminished or restored in astroglia. We found that selective loss of astroglial FMRP contributes to cortical hyperexcitability by enhancing NMDAR-mediated evoked but not spontaneous miniEPSCs and elongating cortical UP state duration. Selective loss of astroglial FMRP is also sufficient to increase locomotor hyperactivity, significantly diminish social novelty preference, and induce memory acquisition and extinction deficits in astroglial Fmr1 cKO mice. Importantly, re-expression of astroglial FMRP is able to significantly rescue the hyperactivity (evoked NMDAR response, UP state duration, and open field test) and social novelty preference in astroglial Fmr1 cON mice. These results demonstrate a profound role of astroglial FMRP in the evoked synaptic signaling, spontaneously occurring cortical UP states, and FXS-related behavioral and learning phenotypes and provide important new insights in the cell type consideration for the FMRP reactivation strategy.

scholarly journals Bacterial agents isolated from cerebrospinal fluid of patients with Acquired Immunodeficiency Syndrome (AIDS) and neurological complications

1994 ◽  
Vol 36 (6) ◽  
pp. 491-496 ◽  
Author(s):  
Ilka Maria Landgraf ◽  
Moisés Palaci ◽  
Maria de Fátima Paiva Vieira ◽  
Sueli Yoko Mizuka Ueki ◽  
Maria Conceição Martins ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Acquired Immunodeficiency Syndrome ◽  
Mycobacterium Avium Complex ◽  
Neurological Complications ◽  
Age Group ◽  
Bacterial Agent ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
And Staphylococcus Aureus ◽  
Culture Positive

Cerebrospinal fluid (CSF) samples from 2083 patients with acquired immunodeficiency syndrome (AIDS) and neurological complications were bacteriologically examined during a period of 7 years (1984-1990). The percentage of patients who had at least one bacterial agent cultured from the CSF was 6.2%. Mycobacterium tuberculosis was the most frequently isolated agent (4.3%), followed by Mycobacterium avium complex or MAC (0.7%), Pseudomonas spp (0.5%), Enterobacter spp (0.4%), and Staphylococcus aureus (0.3%). Among 130 culture positive patients, 89 (68.5%) had M. tuberculosis and 15 (11.6%) had MAC. The frequency of bacterial isolations increased from 1988 (5.2%) to 1990 (7.2%), partly due to the increase in MAC isolations. Bacterial agents were more frequently isolated from patients in the age group 21-30 years and from women (p<0.05).

Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness

1993 ◽  
Vol 264 (6) ◽  
pp. C1367-C1387 ◽  
Author(s):  
M. P. Blaustein
Keyword(s):  
Steady State ◽  
Cell Types ◽  
Whole Body ◽  
Cellular Mechanisms ◽  
Signaling Mechanism ◽  
Physiological Processes ◽  
Endogenous Ouabain ◽  
Adrenal Cortical Hormone ◽  
Salt And Water Balance

Ouabain is a well-known compound but a newly discovered adrenal cortical hormone that plays a role in cell Na+ regulation and in whole body salt and water balance. Ouabain may also be a paracrine hormone and may be secreted by some central nervous system neurons as well as by other types of cells. This article focuses on the cellular mechanisms that underlie the physiological (and pathophysiological) effects of ouabain. Ouabain directly inhibits the plasmalemmal Na+ pump in a variety of cell types. Low ouabain concentrations cause, in the steady state, a modest rise in the cytosolic Na+ concentration but only a minimal decline in membrane potential. All Na+ gradient-dependent processes may thereby be affected, albeit to only a small extent. Most important, however, is the secondary redistribution of Ca2+, mediated by Na(+)-Ca2+ exchange, that should slightly increase the cytosolic free Ca2+ concentration ([Ca2+]cyt). As a result of Ca2+ sequestration in intracellular stores [the endoplasmic and/or sarcoplasmic reticulum (ER/SR)], however, a new steady state is achieved with a slightly increased [Ca2+]cyt but a substantially augmented Ca2+ store; thus the ER/SR effectively acts as a Ca2+ amplifier. This extra stored Ca2+ is then available for mobilization whenever the cells are activated. Cytosolic Ca2+ is a key signaling mechanism in virtually all cells: it controls numerous physiological processes such as contraction, secretion, and excitability. Thus ouabain may modulate cell responsiveness via its influence on ER/SR Ca2+ stores. With these principles in mind, we examine evidence that endogenous ouabain may play a role in numerous physiological and pathophysiological processes associated with altered fluid and electrolyte metabolism and deviations from the normal blood pressure-blood volume relationship. We discuss the possible participation of ouabain in the regulation of vascular tone and then consider the putative role of ouabain in several forms of hypertension, congestive heart failure, thyroid and adrenocortical dysfunction, and diabetes mellitus, as well as in the adaptation to high altitude.

scholarly journals Macropinocytosis in Different Cell Types: Similarities and Differences

Membranes ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 177 ◽  
Author(s):  
Xiao Peng Lin ◽  
Justine D. Mintern ◽  
Paul A. Gleeson
Keyword(s):  
Plasma Proteins ◽  
Physiological Function ◽  
Extracellular Fluid ◽  
Cell Types ◽  
Nutrient Sensing ◽  
Physiological Processes ◽  
Similarities And Differences ◽  
Endocytic Vesicles ◽  
Different Cell Types

Macropinocytosis is a unique pathway of endocytosis characterised by the nonspecific internalisation of large amounts of extracellular fluid, solutes and membrane in large endocytic vesicles known as macropinosomes. Macropinocytosis is important in a range of physiological processes, including antigen presentation, nutrient sensing, recycling of plasma proteins, migration and signalling. It has become apparent in recent years from the study of specialised cells that there are multiple pathways of macropinocytosis utilised by different cell types, and some of these pathways are triggered by different stimuli. Understanding the physiological function of macropinocytosis requires knowledge of the regulation and fate of the macropinocytosis pathways in a range of cell types. Here, we compare the mechanisms of macropinocytosis in different primary and immortalised cells, identify the gaps in knowledge in the field and discuss the potential approaches to analyse the function of macropinocytosis in vivo.

scholarly journals The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

2020 ◽  
Author(s):  
Guoxia Wen ◽  
Tong Zhou ◽  
Wanjun Gu
Keyword(s):  
Liquid Biopsy ◽  
Developmental Stages ◽  
Current Knowledge ◽  
Cell Types ◽  
Circular Rna ◽  
Disease Diagnosis ◽  
Human Diseases ◽  
Biological Functions ◽  
Aberrant Expression ◽  
Physiological Processes

Abstract Circular RNA (circRNA) is a novel class of single-stranded RNAs with a closed loop structure. The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing. Their expression is dynamically regulated and shows spatiotemporal patterns among cell types, tissues and developmental stages. CircRNAs have important biological functions in many physiological processes, and their aberrant expression is implicated in many human diseases. Due to their high stability, circRNAs are becoming promising biomarkers in many human diseases, such as cardiovascular diseases, autoimmune diseases and human cancers. In this review, we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases. We highlight their abundant expression, essential biological functions and significant correlations to human diseases in various components of peripheral blood, including whole blood, blood cells and extracellular vesicles. In addition, we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.

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