scholarly journals Cross-Linked Polymeric Nanogel Formulations of 5‘-Triphosphates of Nucleoside Analogues:  Role of the Cellular Membrane in Drug Release

2005 ◽  
Vol 2 (6) ◽  
pp. 449-461 ◽  
Author(s):  
Serguei V. Vinogradov ◽  
Ekta Kohli ◽  
Arin D. Zeman
Keyword(s):  
Drug Release ◽  
Cellular Membrane ◽  
Nucleoside Analogues

scholarly journals Genogroup II Noroviruses Efficiently Bind to Heparan Sulfate Proteoglycan Associated with the Cellular Membrane

2004 ◽  
Vol 78 (8) ◽  
pp. 3817-3826 ◽  
Author(s):  
Masaru Tamura ◽  
Katsuro Natori ◽  
Masahiko Kobayashi ◽  
Tatsuo Miyamura ◽  
Naokazu Takeda
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Cellular Membrane ◽  
Heparan Sulfate Proteoglycan ◽  
Sulfate Proteoglycan ◽  
Sulfated Glycosaminoglycan ◽  
The Family ◽  
Sulfated Derivative ◽  
Causative Agents

ABSTRACT Norovirus (NV), a member of the family Caliciviridae, is one of the important causative agents of acute gastroenteritis. In the present study, we found that virus-like particles (VLPs) derived from genogroup II (GII) NV were bound to cell surface heparan sulfate proteoglycan. Interestingly, the VLPs derived from GII were more than ten times likelier to bind to cells than were those derived from genogroup I (GI). Heparin, a sulfated glycosaminoglycan, and suramin, a highly sulfated derivative of urea, efficiently blocked VLP binding to mammalian cell surfaces. The reagents known to bind to cell surface heparan sulfate, as well as the enzymes that specifically digest heparan sulfate, markedly reduced VLP binding to the cells. Treatment of the cells with chlorate revealed that sulfation of heparan sulfate plays an important role in the NV-heparan sulfate interaction. The binding efficiency of NV to undifferentiated Caco-2 (U-Caco-2) cells differed largely between GI NV and GII NV, whereas the efficiency of binding to differentiated Caco-2 (D-Caco-2) cells did not differ significantly between the two genogroups, although slight differences between strains were observed. Digestion with heparinase I resulted in a reduction of up to 90% in U-Caco-2 cells and a reduction of up to only 50% in D-Caco-2 cells, indicating that heparan sulfate is the major binding molecule for U-Caco-2 cells, while it contributed to only half of the binding in the case of D-Caco-2 cells. The other half of those VLPs was likely to be associated with H-type blood antigen, suggesting that GII NV has two separate binding sites. The present study is the first to address the possible role of cell surface glycosaminoglycans in the binding of recombinant VLPs of NV.

The Role of Ion Electrophoresis in Electroporation-Mediated Molecular Delivery

2009 ◽  
Author(s):  
Jianbo Li ◽  
Hao Lin
Keyword(s):  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Stem Cell Differentiation ◽  
Equation System ◽  
Cellular Membrane ◽  
Dominant Mode ◽  
Ovary Cells ◽  
Fluorescence Measurements ◽  
Molecular Delivery

Electroporation is a widely applied technique to deliver active molecules into the cellular compartment, to perform tasks such as gene therapy and directed stem cell differentiation, among many others. In this technique, an electric field transiently permeabilizes the cellular membrane to facilitate molecular exchange. While the permeabilization process is relatively well understood, the transport mechanisms for molecular delivery are still under debate. In this work, the role of ion electrophoresis in electroporation-mediated molecular delivery is investigated using numerical simulation. The Nernst-Planck equations for ionic transport in the extracellular and intracellular spaces are solved, respectively, and are coupled through a permeabilization model on the membrane. For the latter, an asymptotic Smoluchowski equation system is adopted, following the work of Krassowska and co-authors. The simulation is used to investigate the delivery of calcium ions into Chinese hamster ovary cells. The results indicate that ion electrophoresis is the dominant mode of transport in the delivery of small charged molecules. Furthermore, the achievable intracellular concentration is strongly influenced by the conductivity difference between the cytoplasm and the buffer, a phenomenon known as “field-amplified sample stacking”. The results agree qualitatively with the fluorescence measurements by Gabriel and Teissie´ (1999), and suggest a new possibility to simultaneously improve cell viability and efficiency in electroporation-mediated molecular delivery.

scholarly journals Functional characterization of the AGL1 aegerolysin in the mycoparasitic fungus Trichoderma atroviride reveals a role in conidiation and antagonism

2020 ◽  
Author(s):  
Mukesh Dubey ◽  
Dan Funck Jensen ◽  
Magnus Karlsson
Keyword(s):  
Pathogenic Fungus ◽  
Functional Characterization ◽  
Fruit Body ◽  
Cellular Membrane ◽  
Plant Diseases ◽  
Wall Material ◽  
Trichoderma Atroviride ◽  
Phenotypic Analysis ◽  
Mycoparasitic Fungus

Abstract Aegerolysins are small secreted pore-forming proteins that are found in both prokaryotes and eukaryotes. The role of aegerolysins in sporulation, fruit body formation, and in lysis of cellular membrane is suggested in fungi. The aim of the present study was to characterize the biological function of the aegerolysin gene agl1 in the mycoparasitic fungus Trichoderma atroviride, used for biological control of plant diseases. Gene expression analysis showed higher expression of agl1 during conidiation and during growth in medium supplemented with cell wall material from the plant pathogenic fungus Rhizoctonia solani as the sole carbon source. Expression of agl1 was supressed under iron-limiting condition, while agl1 transcript was not detected during T. atroviride interactions with the prey fungi Botrytis cinerea or R. solani. Phenotypic analysis of agl1 deletion strains (Δagl1) showed reduced conidiation compared to T. atroviride wild type, thus suggesting the involvement of AGL1 in conidiation. Furthermore, the Δagl1 strains display reduced antagonism towards B. cinerea and R. solani based on a secretion assay, although no difference was detected during direct interactions. These data demonstrate the role of AGL1 in conidiation and antagonism in the mycoparasitic fungus T. atroviride.

scholarly journals Endocytotic Internalization as a Crucial Factor for the Cytotoxicity of Ribonucleases

2007 ◽  
Vol 282 (38) ◽  
pp. 27640-27646 ◽  
Author(s):  
Franziska Leich ◽  
Nadine Stöhr ◽  
Anne Rietz ◽  
Renate Ulbrich-Hofmann ◽  
Ulrich Arnold
Keyword(s):  
Catalytic Activity ◽  
Cellular Uptake ◽  
Cellular Membrane ◽  
Subcellular Fractionation ◽  
Rnase A ◽  
Cytotoxic Action ◽  
Ribonuclease Inhibitor ◽  
Proteolytic Stability ◽  
K 562 Cells

The cytotoxic action of ribonucleases (RNases) requires the interaction of the enzyme with the cellular membrane, its internalization, translocation to the cytosol, and the degradation of ribonucleic acid. The interplay of these processes as well as the role of the thermodynamic and proteolytic stability, the catalytic activity, and the evasion from the intracellular ribonuclease inhibitor (RI) has not yet been fully elucidated. As cytosolic internalization is indispensable for the cytotoxicity of extracellular ribonucleases, we investigated the extent of cytosolic internalization of a cytotoxic, RI-evasive RNase A variant (G88R-RNase A) and of various similarly cytotoxic but RI-sensitive RNase A tandem enzyme variants in comparison to the internalization of the non-cytotoxic and RI-sensitive RNase A. After incubation of K-562 cells with the RNase A variants for 36 h, the internalized amount of RNases was analyzed by rapid cell disruption followed by subcellular fractionation and semiquantitative immunoblotting. The data indicate that an enhanced cellular uptake and an increased entry of the RNases into the cytosol can outweigh the abolishment of catalytic activity by RI. As all RNase A variants proved to be resistant to the proteases present in the different subcellular fractions for more than 100 h, our results suggest that the cytotoxic potency of RNases is determined by an efficient internalization into the cytosol.

The interrelation of the angiotensin and endothelin systems on the modulation of NAD(P)H oxidaseThis paper is one of a selection of papers published in this Special issue, entitled Young Investigator's Forum.

2006 ◽  
Vol 84 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Marc-André Laplante ◽  
Jacques de Champlain
Keyword(s):  
Superoxide Anion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Cellular Membrane ◽  
Kinase C ◽  
Therapeutic Tools ◽  
Produce Superoxide Anion ◽  
Selection Of

The NAD(P)H oxidase is an enzyme assembled at the cellular membrane able to produce superoxide anion from NADH or NAD(P)H (nicotinamide adenine dinucleotide phosphate). It is one of the main sources of superoxide anion in cardiovascular tissues and its role in a variety of cardiovascular disorders such as atherosclerosis, cardiac hypertrophy, and endothelial dysfunction was recently proposed. Although, many factors and receptors were shown to lead to the activation of the enzyme, particulary the type 1 angiotensin receptor, the pathways involved are still widely unknown. Despite the identification of factors such as c-Src and protein kinase C implicated in the acute activation of NAD(P)H oxidase, the signalling involved in the sustained activation of the enzyme is probably far more complex than was previously envisioned. In this review, we describe the role of endothelin-1 in NAD(P)H oxidase signalling after a sustained stimulation by angiotensin II. Since most pathologies caused by an NAD(P)H oxidase overactivation develop over a relatively long period of time, it is necessary to better understand the long-term signalling of the enzyme for the development or use of more specific therapeutic tools.

The role of calcium and cellular membrane dysfunction in experimental trauma and subarachnoid hemorrhage

1985 ◽  
Vol 62 (5) ◽  
pp. 698-703 ◽  
Author(s):  
Otakar R. Hubschmann ◽  
Douglas C. Nathanson
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cellular Membrane ◽  
Membrane Injury ◽  
Content Type ◽  
Experimental Trauma ◽  
Acute Subarachnoid Hemorrhage ◽  
A Chain ◽  
The Moment ◽  
Large Vessels

✓ Acute subarachnoid hemorrhage (SAH) and intraparenchymal hematoma (IPH) in cats are accompanied by massive cellular depolarization. This depolarization, characterized by potassium (K+) efflux and calcium (Ca++) influx, results in membrane destabilization, osmotic imbalance, and a decrease in electrical conduction. The Ca++ influx appears to initiate a chain reaction that, in some instances, may result in delayed cell destruction. The ionic dysequilibrium probably contributes to both brain engorgement and spasm in large vessels. The cellular depolarization and calcium-induced cell membrane injury at the moment of impact may play a greater role in the pathophysiology of head trauma than previously thought.

scholarly journals P4-199: Role of γ secretase in the cellular membrane lipid composition

2008 ◽  
Vol 4 ◽  
pp. T729-T730
Author(s):  
Jessica Hommes ◽  
Jochen Walter ◽  
Bernadette Breiden ◽  
Irfan Y. Tamboli ◽  
Günter Schwarzmann
Keyword(s):  
Lipid Composition ◽  
Cellular Membrane ◽  
Membrane Lipid ◽  
Membrane Lipid Composition

scholarly journals A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication

2008 ◽  
Vol 4 (11) ◽  
pp. e1000216 ◽  
Author(s):  
George A. Belov ◽  
Qian Feng ◽  
Krisztina Nikovics ◽  
Catherine L. Jackson ◽  
Ellie Ehrenfeld
Keyword(s):  
Critical Role ◽  
Membrane Traffic ◽  
Rna Replication ◽  
Cellular Membrane

Role of Ubiquitylation in Cellular Membrane Transport

2006 ◽  
Vol 86 (2) ◽  
pp. 669-707 ◽  
Author(s):  
Olivier Staub ◽  
Daniela Rotin
Keyword(s):  
Membrane Proteins ◽  
Mammalian Cells ◽  
Secretory Pathway ◽  
Surface Expression ◽  
Cellular Membrane ◽  
Cell Surface Expression ◽  
Multivesicular Bodies ◽  
The Past ◽  
Endoplasmic Reticulum Associated Degradation

Ubiquitylation of membrane proteins has gained considerable interest in recent years. It has been recognized as a signal that negatively regulates the cell surface expression of many plasma membrane proteins both in yeast and in mammalian cells. Moreover, it is also involved in endoplasmic reticulum-associated degradation of membrane proteins, and it acts as a sorting signal both in the secretory pathway and in endosomes, where it targets proteins into multivesicular bodies in the lumen of vacuoles/lysosomes. In this review we discuss the progress in understanding these processes, achieved during the past several years.

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