			Home About us Contact

Monolayer Permeability (monolayer + permeability)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Formation of lipid raft redox signalling platforms in glomerular endothelial cells: an early event of homocysteine-induced glomerular injury

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009
Fan Yi
Abstract The present study tested the hypothesis that homocysteine (Hcys)-induced ceramide production stimulates lipid rafts (LRs) clustering on the membrane of glomerular endothelial cells (GECs) to form redox signalling platforms by aggregation and activation of NADPH oxidase subunits and thereby enhances superoxide (O2.,) production, leading to glomerular endothelial dysfunction and ultimate injury or sclerosis. Using confocal microscopy, we first demonstrated a co-localization of LR clusters with NADPH oxidase subunits, gp91phox and p47phox in the GECs membrane upon Hcys stimulation. Immunoblot analysis of floated detergent-resistant membrane fractions found that in LR fractions NADPH oxidase subunits gp91phox and p47phox are enriched and that the activity of this enzyme dramatically increased. We also examined the effect of elevated Hcys on the cell monolayer permeability in GECs. It was found that Hcys significantly increased GEC permeability, which was blocked by inhibition of LR redox signalling platform formation. Finally, we found that Hcys-induced enhancement of GEC permeability is associated with the regulation of microtubule stability through these LR-redox platforms. It is concluded that the early injurious effect of Hcys on the glomerular endothelium is associated with the formation of redox signalling platforms via LR clustering, which may lead to increases in glomerular permeability by disruption of microtubule network in GECs. [source]

Nitric oxide modulation of low-density mononuclear cell transendothelial migration

MICROSURGERY, Issue 5 2005
J.S. Isenberg M.D., M.P.H.
The blood-endothelial cell interface is a region of significant importance in many physiologic and pathologic processes. Blood-borne macromolecules and cells gain access to the subendothelial space and extravascular tissues by traversing the endothelium. Yet the various factors responsible for modulation of this process remain only partially elucidated. Several agents were found to be involved in this process, including nitric oxide (NO) and vascular endothelial growth factor (VEGF). It is known that under stress conditions (e.g., inflammation), NO can modulate the permeability of endothelial-cell monolayers to low-density mononuclear cells (LDMNCs). However, it is not known if NO can modulate such effects in the absence of inflammatory stimulation. In the present study, we utilized a Transwell chamber model to examine endothelial-cell monolayer permeability to LDMNCs in the absence of inflammatory stimuli. We noted that NO donor and L-arginine increased transendothelial-cell migration, whereas nitric oxide synthase (NOS) inhibition decreased migration. These effects were not significantly abrogated by VEGF antibody, suggesting that they were not VEGF-dependent. © 2005 Wiley-Liss, Inc. Microsurgery 25:452,456, 2005. [source]

Epidermal growth factor receptor and claudin-2 participate in A549 permeability and remodeling: Implications for non-small cell lung cancer tumor colonization

MOLECULAR CARCINOGENESIS, Issue 6 2009
Yakov Peter
Abstract Tumor colonization involves changes in cell permeability and remodeling. Paracellular permeability is regulated by claudins, integrated tight junction (TJ) proteins, located on the apicolateral portion of epithelial cells. Epidermal growth factor (EGF) was reported to modify cellular claudin levels and induce remodeling. To investigate a role for EGF receptor (EGFR) activation in tumor colonization we studied the effect of EGF and claudin-2 overexpression on permeability and cell reorganization in the human A549 non-small cell lung cancer (NSCLC) cell line. Our data demonstrated that A549 cells possess functional TJs and that EGF treatment increased levels of claudin-2 expression by 46%. Furthermore, EGFR signaling reduced monolayer permeability to choline and triggered cellular remodeling. The mitogen-activated protein kinase inhibitor PD98059 blocked the effect on A549 permeability and remodeling. EGF stimulation also exacerbated a fourfold increase in cell colonization elicited by claudin-2 upregulation. Our findings are consistent with the hypothesis that EGFR signaling plays an important role in A549 cell physiology and acts synergistically with claudin-2 to accelerate tumor colonization. Understanding the influence of EGF on A549 cell permeability and reorganization will help shed light on NSCLC tumor colonization and contribute to the development of novel anti-cancer treatments. © 2008 Wiley-Liss, Inc. [source]

Monocyte-Induced Endothelial Calcium Signaling Mediates Early Xenogeneic Endothelial Activation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2005
Mark D. Peterson
Hallmarks of delayed xenograft rejection include monocyte infiltration, endothelial cell activation and disruption of the endothelial barrier. The monocyte is an important initiator of this type of rejection because monocytes accumulate within hours after xenografting and prior monocyte depletion suppresses the development of this type of rejection. However, the mechanisms that mediate monocyte-induced xenograft injury are unclear at present. Here we report that human monocytes activate xenogeneic endothelial cells through calcium signals. Monocyte contact with porcine but not human endothelium leads to an endothelial calcium transient mediated via a G-protein-coupled receptor (GPCR) that results in up-regulation of porcine VCAM-1 and E-selectin. Although human monocyte adhesion was greater to porcine than to human endothelium, especially when studied under laminar flow, blockade of the xeno-specific endothelial calcium signals did not reduce adhesion of human monocytes to porcine endothelium. Human monocyte contact to porcine endothelium also resulted in reorganization of the F-actin cytoskeleton with a concomitant increase in endothelial monolayer permeability. In contrast to the effect on adhesion, these changes appear to be regulated through endothelial calcium signals. Taken together, these data suggest that human monocytes are capable of activating xenogeneic endothelial cells through calcium transients, as well as other distinct pathways. [source]

Curcumin inhibits reactive oxygen species formation and vascular hyperpermeability following haemorrhagic shock

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2010
Binu Tharakan
Summary 1. Oxidative stress induced by reactive oxygen species (ROS) is a key mediator of haemorrhagic shock (HS)-induced vascular hyperpermeability. In the present study, curcumin, a natural anti-oxidant obtained from turmeric (Curcuma longa), was tested against HS-induced hyperpermeability and associated ROS formation in rat mesenteric post-capillary venules in vivo and in rat lung microvascular endothelial cells (RLMEC) in vitro. 2. In rats, HS was induced by withdrawing blood to reduce mean arterial pressure to 40 mmHg for 60 min, followed by resuscitation for 60 min. To investigate vascular permeability, rats were given fluorescein isothiocyanate (FITC),albumin (50 mg/kg, i.v.). The FITC,albumin flux was measured in mesenteric post-capillary venules by determining optical intensity intra- and extravascularly under intravital microscopy. Mitochondrial ROS formation was determined using dihydrorhodamine 123 in vivo. Parallel studies were conducted in vitro using serum collected after HS. The serum was tested on rat lung microvascular endothelial cell RLMEC monolayers. 3. In rats, HS induced a significant increase in vascular hyperpermeability and ROS formation in vivo (P < 0.05). Treatment with curcumin (20 ,mol/L) attenuated both these effects (P < 0.05). In RLMEC in vitro, HS serum induced monolayer permeability and ROS formation. Curcumin (10 ,mol/L) attenuated HS serum-induced monolayer hyperpermeability and ROS formation. Curcumin (2,100 ,mol/L) scavenged 2,2,-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and 1,1-diphenyl-2-picrylhydrazyl radicals in vitro, indicating its potential as a free radical scavenger. 4. The present study demonstrates that curcumin is an inhibitor of vascular hyperpermeability following HS, with its protective effects mediated through its anti-oxidant properties. [source]