Evidence for post-translational processing of vascular endothelial (VE)-cadherin in brain tumors: towards a candidate biomarker.

Vessel abnormalities are among the most important features in malignant glioma. Vascular endothelial (VE)-cadherin is of major importance for vascular integrity. Upon cytokine challenge, VE-cadherin structural modifications have been described including tyrosine phosphorylation and cleavage.

Protocadherin-12 cleavage is a regulated process mediated by ADAM10 protein: evidence of shedding up-regulation in pre-eclampsia.

Protocadherins are a group of transmembrane proteins with homophilic binding activity, members of the cadherin superfamily. Apart from their role in adhesion, the cellular functions of protocadherins are essentially unknown. Protocadherin (PCDH)12 was previously identified in invasive trophoblasts and endothelial and mesangial cells in the mouse.

Protocadherin 12 deficiency alters morphogenesis and transcriptional profile of the placenta.

Protocadherins are transmembrane proteins exhibiting homophilic adhesive activities through their extracellular domain. Protocadherin 12 (Pcdh12) is expressed in angiogenic endothelial cells, mesangial cells of kidney glomeruli, and glycogen cells of the mouse placenta. To get insight into the role of this protein in vivo, we analyzed PCDH12-deficient mice and investigated their placental phenotype.

Src kinase phosphorylates vascular endothelial-cadherin in response to vascular endothelial growth factor: identification of tyrosine 685 as the unique target site.

Src-family tyrosine kinases are regulatory proteins that play a pivotal role in the disorganization of cadherin-dependent cell-cell contacts. We previously showed that Src was associated with vascular endothelial (VE)-cadherin and that tyrosine phosphorylation level of VE-cadherin was dramatically increased in angiogenic tissues as compared to quiescent tissues. Here, we examined whether VE-cadherin was a direct substrate for Src in vascular endothelial growth factor (VEGF)-induced VE-cadherin phosphorylation, and we identified the target tyrosine sites.

Decreased circulating elastin peptide levels in humans with sepsis.

Objective: Sepsis is a potentially life-threatening medical condition induced by viral, bacterial or fungal infection, which is characterized by systemic inflammation, hypotension and vasodilation that can lead to cardiovascular collapse. Increased activity of elastases, enzymes which degrade the extracellular matrix components including elastin, has been demonstrated in plasma of septic patients. Since elastin peptides (EP), by binding to an elastin-laminin receptor on vascular endothelial and smooth muscle cells, induce dose-dependent vasodilation, we hypothesized that elevated circulating EP could contribute to the vasodilation that occurs in septic patients.

Vascular endothelial-cadherin tyrosine phosphorylation in angiogenic and quiescent adult tissues.

Vascular endothelial-cadherin (VE-cadherin) plays a key role in angiogenesis and in vascular permeability. The regulation of its biological activity may be a central mechanism in normal or pathological angiogenesis. VE-cadherin has been shown to be phosphorylated on tyrosine in vitro under various conditions, including stimulation by VEGF.

Highly protective effects of chronic oral administration of nicorandil on the heart of ageing rats.

1. We have tested the effects of 2 month oral treatment with the KATP opener, nitric oxide (NO) donor and anti-oxidant molecule nicorandil (0.1 mg/kg per day) on major physiological parameters and heart function of 4-, 12- and 24-month-old rats.

Identification of membrane calcium channels essential for cytoplasmic and nuclear calcium elevations induced by vascular endothelial growth factor in human endothelial cells.

Vascular endothelial growth factor (VEGF) is mitogenic for endothelial cells and has been shown to induce angiogenesis and endothelial cell migration through stimulation of endothelial tyrosine-kinase receptors. Here, using confocal microscopy and the patch-clamp technique on endothelial cells, membrane permeability to calcium as well as cytoplasmic and nuclear free calcium levels have been investigated in the first stages of tyrosine-kinase receptor activation by VEGF. VEGF (0.

Stimulation of platelet-activating factor (PAF) receptors increases inositol phosphate production and cytosolic free Ca2+ concentrations in N1E-115 neuroblastoma cells.

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine, PAF) has recently been recognized as an important mediator in the pathophysiology of brain injury. This study demonstrates that, in suspended populations of N1E-115 cells loaded with Indo-1, biologically relevant concentrations of PAF produce a rapid and transient elevation in cytosolic free calcium concentration ([Ca2+]i). Moreover, nanomolar concentrations of PAF increase [3H]-inositol phosphate production.

An experimental model of hypoxia on isolated rat heart in recirculating system: study of fatty acid metabolism with an iodinated fatty acid.

An experimental model of hypoxia was developed on isolated rat heart to study the effects of hypoxia on cardiac performance and metabolism. Fatty acid (FA) metabolism was explored by external detection with a labelled FA, iodohexadecenoic acid (IHA). Hearts, after 30 min preperfusion in an open system, were transferred in a recirculating system for 40 min and perfused with oleate, glucose, lactate, pyruvate and IHA, either in normoxia (pO2 = 660 mmHg) or in hypoxia (pO2 = 220 mmHg).

Influence of fatty acid backdiffusion on compartmental analysis of external detection curves obtained with 123-iodohexadecenoic acid in isolated rat heart.

In isolated rat hearts, we investigated a possible backdiffusion of fatty acids and tried to determine whether it impaired our compartmental analysis of myocardial time-radioactivity curves obtained with an iodinated fatty acid, 16-iodo-9-hexadecenoic acid (IHA). Backdiffusion was not observed directly in the coronary effluents but was estimated by analysis of the external detection curves. Furthermore, when backdiffusion was not taken into account in the mathematical analysis, we obtained similar data on IHA intramyocardial metabolism.

Effect of short-term fasting on [123I] iodohexadecenoic acid metabolism in the isolated perfused rat heart. Validation of mathematical model by comparison with experimental measurements.

In order to study metabolic modifications induced by short term fasting and their consequences on the uptake and intracellular fate of fatty acids iodine labelled in omega position, rats undergo a 36h fasting. Hearts are perfused in a Langendorff system with a glucose (11 mM) perfusion medium; [123I] hexadecenoic acid (IHA) is injected as a bolus. A comparison between time-activity curves p.

Age-dependent differences in energetic status, electrical and mechanical performance of rat myocardium.

Transmembrane action potential (AP), isotonic contraction and biochemical measurements were performed in 12-day, 1-, 3-, 14- and 24-month-old rat hearts. The major findings of this study are: (1) the AP and contraction duration decrease between 12 days and 1 month of age (growth period) and increase between 1 month and 24 months of age; (2) as compared with 1 month and 14 months, respectively, isotonic contraction peak shortening is lower at 12 days and 24 months of age; (3) the phosphorylation potential is higher during the postnatal period and decreases in an age-correlated manner; (4) the inorganic phosphate and glycogen contents are higher in the senescent heart. We conclude that, during the postnatal period the particular AP and the lower mechanical performances could be the result of immature sarcolemma and sarcoplasmic reticulum properties rather than modifications in the oxidative phosphorylation mechanism and by contrast, in senescent heart, that AP and contraction modifications could result from metabolic modifications.

Superoxide dismutase, glutathione peroxidase, catalase, and lipid peroxidation in the major organs of the aging rats.

Glutathione peroxidase (GSh-Px), superoxide dismutase (SOD), catalase (CAT) activities and malon-dialdehyde (MDA) content were determined in heart, liver, kidney and brain of rats. Two different age groups (4 months; 24 months) were considered. GSH-Px and SOD activities decrease significantly for the aged liver and kidney.

Effects of clofibrate and tiadenol on the elimination of lipids and bile acids in rat bile.

The aim of the work presented here was to compare the biliary elimination of cholesterol and the different bile acids of rats that had been made hypolipidemic by short-term treatments with clofibrate or tiadenol. Both treatments induced a significant decrease in cholesterol output in the bile. The analysis of the different bile acids showed a decrease in dihydroxylated acids elimination (especially CDC acid) without any difference between the 2 sexes.