Search results for "cell membrane"
showing 10 items of 635 documents
Membrane topology of gp41 and amyloid precursor protein: Interfering transmembrane interactions as potential targets for HIV and Alzheimer treatment
2009
AbstractThe amyloid precursor protein (APP), that plays a critical role in the development of senile plaques in Alzheimer disease (AD), and the gp41 envelope protein of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), are single-spanning type-1 transmembrane (TM) glycoproteins with the ability to form homo-oligomers. In this review we describe similarities, both in structural terms and sequence determinants of their TM and juxtamembrane regions. The TM domains are essential not only for anchoring the proteins in membranes but also have functional roles. Both TM segments contain GxxxG motifs that drive TM associations within the li…
Cloning and characterization of Scavidin, a fusion protein for the targeted delivery of biotinylated molecules.
2001
We have constructed a novel fusion protein "Scavidin" consisting of the macrophage scavenger receptor class A and avidin. The Scavidin fusion protein is transported to plasma membranes where the avidin portion of the fusion protein binds biotin with high affinity and forms the basis for the targeted delivery of biotinylated molecules. Subcellular fractionation analysis, immunostaining, and electron microscopy demonstrated endosomal localization of the fusion protein. According to pulse-labeling and cross-linking studies Scavidin is found as monomers (55 kDa), dimers, and multimers, of which the 220-kDa form was the most abundant. The biotin binding capacity and active endocytosis of the bio…
Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Bisoprolol Fumarate
2014
Abstract Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (Inter…
Impact of ticagrelor on P2Y1 and P2Y12 localization and on cholesterol levels in platelet plasma membrane
2017
Ticagrelor is an antiplatelet agent that inhibits platelet activation via P2Y12 antagonism. There are several studies showing that P2Y12 needs lipid rafts to be activated, but there are few data about how ticagrelor impacts lipid raft organization. Therefore, we aimed to investigate how ticagrelor could impact the distribution of cholesterol and consequently alter the organization of lipid rafts on platelet plasma membranes. We identified cholesterol-enriched raft fractions in platelet membranes by quantification of their cholesterol levels. Modifications in cholesterol and protein profiles (Flotillin 1, Flotillin 2, CD36, P2Y1, and P2Y12) were studied in platelets stimulated by ADP, treate…
Identifying human platelet glycoproteins IIb and IIIa by capillary electrophoresis.
1998
Glanzmann thrombasthenia (GT) is an inherited hemorrhagic defect due to a failure of the platelet membrane glycoprotein (GP) IIb–IIIa complex. Capillary electrophoresis (CE) analysis of solubilized platelet membranes from normal individuals showed the presence of two peaks with a migration time of 27 and 29 min, respectively. An excellent run-to-run and day-to-day reproducibility of the technique (< 1% variation of the retention time) was documented. Using an automated Ferguson method, the apparent molecular masses were 100.0 kDa and 138.5 kDa, respectively. Immunoprecipitation with monoclonal antibodies anti-GP IIIa (B59.2.1) and anti-IIb (61.9.1.3) showed the two peaks as IIIa and IIb, re…
Clonidine increases membrane-associated phospholipase A2
2005
Background and objective: An anti-inflammatory effect of α 2 -adrenoreceptor agonists has been suggested. Phospholipase A 2 is a key enzyme in the production of precursors of inflammatory lipid mediators. The aim of the present study was to investigate the effect of clonidine on phospholipase A 2 activity in an established in vitro model. Methods: Human being platelet membranes containing active phospholipase A 2 were exposed to buffer control or to three increasing concentrations of clonidine. Phospholipase A 2 was measured by a radioisotope technique. Results: A massive increase in phospholipase A 2 activity was measured after clonidine exposure leading to final values of 92.5 ′ 3.1 pmol …
Activation of cGMP-dependent Protein Kinase Iβ Inhibits Interleukin 2 Release and Proliferation of T Cell Receptor-stimulated Human Peripheral T Cells
2000
Several major functions of type I cGMP-dependent protein kinase (cGK I) have been established in smooth muscle cells, platelets, endothelial cells, and cardiac myocytes. Here we demonstrate that cGK Ibeta is endogenously expressed in freshly purified human peripheral blood T lymphocytes and inhibits their proliferation and interleukin 2 release. Incubation of human T cells with the NO donor, sodium nitroprusside, or the membrane-permeant cGMP analogs PET-cGMP and 8-pCPT-cGMP, activated cGK I and produced (i) a distinct pattern of phosphorylation of vasodilator-stimulated phosphoprotein, (ii) stimulation of the mitogen-activated protein kinases ERK1/2 and p38 kinase, and, upon anti-CD3 stimu…
Anti-oxidative effects and harmlessness of asymmetric Au@Fe3O4 Janus particles on human blood cells
2014
AbstractThe physical properties of asymmetric Janus particles are highly promising for future biomedical applications. However, only a few data is available on their biological impact on human cells. We investigated the biological impact of different Au@Fe3O4 Janus particle formulations in vitro to analyse specific uptake modalities and their potential cytotoxic effects on human cells of the blood regarding intravenous injection. We demonstrate that Au@Fe3O4 Janus particles exhibit a similar or even better biocompatibility compared to the well-studied spherical iron oxide nanoparticles. The impact of Janus particles on cells depends mainly on three factors. (1) Surface functionalization: NH…
DHEA-Bodipy–a functional fluorescent DHEA analog for live cell imaging
2009
International audience; The androgen dehydroepiandrosterone (DHEA) has been reported to protect neuronal cells against dysfunction and apoptosis. Several signaling pathways involved in these effects have been described but little is known about the intracellular trafficking of DHEA. We describe design, synthesis and characterization of DHEA-Bodipy, a novel fluorescent DHEA analog. DHEA-Bodipy proved to be a functional DHEA derivative: DHEA-Bodipy (i) induced estrogen receptor α-mediated gene activation, (ii) protected PC12 rat pheochromocytoma cells against serum deprivation-induced apoptosis, and (iii) induced stress fibers and focal adhesion contacts in SH-SY5Y human neuroblastoma cells. …
Encapsulation capacity and natural payload delivery of an anticancer drug from boron nitride nanotube.
2016
The behavior of confined anticancer carboplatin (CPT) molecules in a single (10, 10) boron nitride nanotube (BNNT) was studied by means of molecular dynamics simulations. Our study revealed a very large storage capacity of BNNT. Analysis of the energy profiles depending on the number of confined molecules, and on their spatial organization allowed us to quantify the ability of BNNT to vectorize CPT. Indeed, BNNT despite its small radius presented a large inner volume that favored stable encapsulation of multiple active anticancer molecules. Moreover, in our molecular dynamics simulations, the empty BNNT and the BNNT filled with CPT diffused spontaneously to the cell membrane and were able t…