Search results for "Cell Membrane Permeability"
showing 10 items of 101 documents
Staphylococcus aureus α-toxin: small pore, large consequences
2018
Abstract The small β-pore-forming α-toxin, also termed α-hemolysin or Hla is considered to be an important virulence factor of Staphylococcus aureus. Perforation of the plasma membrane (PM) by Hla leads to uncontrolled flux of ions and water. Already a small number of toxin pores seems to be sufficient to induce complex cellular responses, many of which depend on the efflux of potassium. In this article, we discuss the implications of secondary membrane lesions, for example, by endogenous channels, for Hla-mediated toxicity, for calcium-influx and membrane repair. Activation of purinergic receptors has been proposed to be a major contributor to the lytic effects of various pore forming prot…
Tight Junctions as a Key for Pathogens Invasion in Intestinal Epithelial Cells
2021
Tight junctions play a major role in maintaining the integrity and impermeability of the intestinal barrier. As such, they act as an ideal target for pathogens to promote their translocation through the intestinal mucosa and invade their host. Different strategies are used by pathogens, aimed at directly destabilizing the junctional network or modulating the different signaling pathways involved in the modulation of these junctions. After a brief presentation of the organization and modulation of tight junctions, we provide the state of the art of the molecular mechanisms leading to permeability breakdown of the gut barrier as a consequence of tight junctions’ attack by pathogens, including…
Transcriptomic study of the toxic mechanism triggered by beauvericin in Jurkat cells
2018
Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to increase oxidative stress by altering membrane ion permeability and uncoupling oxidative phosphorylation. A toxicogenomic study was performed to investigate gene expression changes triggered by BEA exposure (1.5, 3 and 5 mu M; 24 h) in Jurkat cells through RNA-sequencing and differential gene expression analysis. Perturbed gene expression was observed in a concentration dependent manner, with 43 differentially expressed genes (DEGs) overlapped in the three studied concentrations. Gene ontology (GO) analysis showed several biological processes related to electron transport chain, oxidative phosphorylation, and cel…
Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix.
2012
Purpose: This study investigated the absorption mechanism of the phytochemicals indicaxanthin and betanin and the influence of their food matrix (cactus pear and red beet) on the intestinal transport. Methods: Trans-epithelial transport of dietary-consistent amounts of indicaxanthin and betanin in Caco-2 cell monolayers seeded on TranswellR inserts was measured in apical to basolateral (AP-BL) and basolateral to apical (BL-AP) direction, under an inwardly directed pH gradient (pH 6.0/7.4, AP/BL) mimicking luminal and serosal sides of human intestinal epithelium. The effect of inhibitors of membrane transporters on the absorption was also evaluated. Contribution of the paracellular route was…
Skin-PAMPA: a new method for fast prediction of skin penetration.
2011
The goal of this study was to develop a quick, reliable, and cost-effective permeability model for predicting transdermal penetration of compounds. The Parallel Artificial Membrane Permeability Assay (PAMPA) was chosen for this purpose, as it already has been successfully used for estimating passive gastrointestinal absorption and blood-brain barrier permeability. To match the permeability of the rate-limiting barrier in human skin, synthetic certramides, which are analogs of the ceramides present in the stratum corneum, were selected for the skin-PAMPA model. The final skin-PAMPA membrane lipid mixture (certramide, free fatty acid, and cholesterol) was selected and optimized based on data …
Effect of ouabain and furosemide on erythrocyte sodium and phosphate transport.
1981
The effects of ouabain and furosemide on the unidirectional efflux of sodium and phosphate ions were studied in freshly drawn human red blood cells (RBCs). In the presence of physiologic concentrations of sodium and potassium the rate of sodium efflux was reduced by 74% due to ouabain sensitivity. Furosemide (1.0 mmol/l) reduced ouabain-insensitive sodium transport rate by a further 50%. Thus, 13% of total sodium efflux was inhibited by furosemide when ouabain was present. In the absence of ouabain, however, furosemide inhibited 31% of total sodium transport, indicating that it also affected ouabain-sensitive sodium efflux. Phosphate transfer of RBCs was almost 1.0 mmol/l RBCs per hour. Ery…
Microalbuminuria fractional clearance and early renal permselectivity changes in essential hypertension.
1992
In order to verify if, in essential hypertension (EH), the microalbuminuria (AER) increase could be due to hemodynamic modifications or to glomerular structural changes, in 15 essential hypertensives (EHs) with 24-hour AER16 micrograms/min and in 15 EHs with 24-hour AERor = 16 micrograms/min, the day- and nighttime behavior of creatinine clearance (Ccr), as well as AER clearance (AER-C) and fractional clearance (AER-FC), and behavior of blood pressure (BP) was evaluated. Patients with 24-hour AER16 micrograms/min showed significantly higher values of 24-hour and daytime Ccr than the other group of EHs, while during the night period, there were no significant differences between the two grou…
Prostacyclin receptor desensitization is a reversible phenomenon in human platelets.
1997
Background Long-term exposure of platelets to endogenous or exogenous prostacyclin or its analogues might result in desensitization of the platelet prostacyclin receptor in vitro and in vivo accompanied by a loss in receptor density on the platelet surface and a reduced sensitivity toward the inhibitory effects of prostacyclins. However, the reversibility of this process in platelets has not yet been investigated. Methods and Results Human platelets desensitized by the chemically stable prostacyclin analogue iloprost showed a significant reduction in [ 3 H]-iloprost binding sites that was reversed by saponin permeabilization. This indicates functionally active internalized prostacyclin rec…
Conductance and Ion Selectivity of a Mesoscopic Protein Nanopore Probed with Cysteine Scanning Mutagenesis
2005
Nanometer-scale proteinaceous pores are the basis of ion and macromolecular transport in cells and organelles. Recent studies suggest that ion channels and synthetic nanopores may prove useful in biotechnological applications. To better understand the structure-function relationship of nanopores, we are studying the ion-conducting properties of channels formed by wild-type and genetically engineered versions of Staphylococcus aureus alpha-hemolysin (alphaHL) reconstituted into planar lipid bilayer membranes. Specifically, we measured the ion selectivities and current-voltage relationships of channels formed with 24 different alphaHL point cysteine mutants before and after derivatizing the c…
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…