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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spatial position of astrocytes between neurons and the vascular endothelium might allow the astrocytic syncytium to act as a pathway for diffusion or active transport of substances between the environment of neurons and the cerebral blood vessels and ventricles. Furthermore, the intimate morphological arrangements between astrocytes and neurons might reflect biochemical cooperations between the cells. Astrocytes in the adult nervous system are in an unique position to regulate the environment of neurons and thereby their sensitivity. Some questions are raised: How do astrocytes receive neuronal signals? Are there local populations of astrocytes which respond specifically to small groups of neurons? Late results suggesting astrocytes to be a candidate for the supervision of neurotransmission are commented upon.
Cell Mol Biol 1990
PMID:Astrocytes in neurotransmission. A review. 196 74

Myocardial ischemia is associated with profound electrophysiologic derangements which occur within minutes and are rapidly reversible with reperfusion, suggesting that subtle and reversible biochemical alterations within or near the sarcolemma contribute. Our efforts have concentrated on two structurally similar amphipathic metabolites, long-chain acylcarnitine and lysophosphatidylcholine. Studies performed in vitro in isolated tissue indicate that incorporation of either metabolite into the sarcolemma at concentrations of 1-2 mole %, as verified using electron microscopic (EM) autoradiography, elicits profound electrophysiologic derangements analogous to those seen in the ischemic heart in vivo. In isolated myocytes in vitro, the electrophysiologic derangements elicited by hypoxia are associated with a marked 70-fold increase in the endogenous sarcolemmal accumulation of long-chain acylcarnitine. Inhibition of carnitine acyltransferase I (CAT-I) not only prevents the accumulation of long-chain acylcarnitine in isolated myocytes exposed to severe hypoxia, but also markedly attenuates the electrophysiologic alterations. Several lines of experimental evidence, including measurements in venous effluents as well as cardiac lymph, indicate that lysophosphatidylcholine (LPC) accumulates to a large extent in the extracellular space during ischemia. This extracellular accumulation may be secondary to release from vascular endothelium, smooth muscle or blood cell elements. In crude homogenates of myocardial tissue, the total enzymic activity for catabolism of LPC far exceeds the total activity for synthesis of LPC mediated by phospholipase A2 (PLA2) catalyzed hydrolysis of phosphatidylcholine (PC). Therefore, inhibition of catabolism would be required for net accumulation of LPC to occur. Three enzymes responsible for the catabolism of LPC are inhibited by either long-chain acylcarnitine or acidic pH. Thus, accumulation of long-chain acylcarnitine and acidosis contribute to the increase in LPC observed in ischemic tissue. In this report, we provide evidence that accumulation of long-chain acylcarnitine occurs very rapidly in ischemic myocardium in vivo, coincident with the development of electrophysiologic alterations leading to malignant arrhythmias as verified using 3-dimensional cardiac mapping procedures. Following a brief, 2-min period of ischemia, long-chain acylcarnitine content increased four-fold in the ischemic region, concomitant with the development of electrophysiologic abnormalities observed during this period. Additionally, we demonstrate that modification of intracellular lipolysis by beta-adrenergic receptor stimulation or blockade does not influence long-chain acylcarnitine accumulation following this 2-min interval of ischemia. These results suggest that production of long-chain acylcarnitine is not limited by the intracellular free fatty acid concentration early in ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Cardiol 1991 Feb
PMID:Amphipathic lipid metabolites and their relation to arrhythmogenesis in the ischemic heart. 203 71

Chemotactic peptides in the circulation stimulate neutrophils to become sequestered in the pulmonary vasculature, and low concentrations of bacterial lipopolysaccharide (LPS) enhance and prolong this effect. This interaction of neutrophils with the vascular endothelium is thought to involve, in part, the increase in adhesiveness induced in neutrophils by such stimuli. In this study, the binding of albumin-coated latex beads to neutrophils was used to determine whether the enhancement seen with LPS results from an increase in the number of adhesive cells, from the enhancement of the adhesiveness of individual neutrophils, or both. Chemotactic peptides alone and LPS alone induced an increase both in the adhesive population and in the number of beads bound per individual neutrophil. The number of beads bound per cell increased over a very wide range of stimulus concentrations, showing that the degree of adhesiveness of an individual cell in the population varies over a considerable range. Trace concentrations of LPS (10 ng/ml or less), i.e., levels close to those measurable in vivo, had little effect on the proportion of neutrophils that were stimulated by chemotactic factor to become adhesive but did significantly enhance the number of beads bound to each individual neutrophil. The enhancement may require the presence of the CD11/18 glycoprotein complex, but was not further upregulated by LPS. No evidence could be obtained to suggest that the effect of LPS involved release of tumor necrosis factor (TNF) from the numbers of monocytes in the preparation, and the observations are consistent with a direct effect of LPS on the neutrophils. It is suggested that this increase in adhesive sites on the cell could explain the persistence of the sequestration of neutrophils in the microvasculature seen in the presence of both chemoattractants and LPS by enhancing the "strength" of the adhesion to endothelial cells. The increased adhesion may also set the stage for enhanced endothelial injury.
Am J Respir Cell Mol Biol 1990 Jun
PMID:Interaction between chemoattractants and bacterial lipopolysaccharide in the induction and enhancement of neutrophil adhesion. 218 56

We have previously described the cloning of a group of novel cellular immediate-early response genes whose expression in human umbilical vein endothelial cells is induced by tumor necrosis factor alpha in the presence of cycloheximide. These genes are likely to participate in mediating the response of the vascular endothelium to proinflammatory cytokines. In this study, we further characterized one of these novel gene products named B61. Sequence analysis of cDNA clones encoding B61 revealed that its protein product has no significant homology to previously described proteins. Southern analysis suggested that B61 is an evolutionarily conserved single-copy gene. B61 is primarily a hydrophilic molecule but contains both a hydrophobic N-terminal and a hydrophobic C-terminal region. The N-terminal region is typical of a signal peptide, which is consistent with the secreted nature of the protein. The mature form of the predicted protein consists of 187 amino acid residues and has a molecular weight of 22,000. Immunoprecipitation of metabolically labeled human umbilical vein endothelial cell preparations revealed that B61 is a 25-kilodalton secreted protein which is markedly induced by tumor necrosis factor.
Mol Cell Biol 1990 Nov
PMID:A novel immediate-early response gene of endothelium is induced by cytokines and encodes a secreted protein. 223 19

Hydrogen peroxide (H2O2) has been implicated in cardiac damage due to ischemia and reperfusion. We adapted an electron microscopic, histochemical method for demonstrating H2O2 produced by isolated cells to isolated, buffer-perfused rabbit hearts. The method involves formation of an electron-dense precipitate when H2O2 reacts with cerium chloride (CeCl3). We perfused hearts retrograde via the aorta with well-oxygenated bicarbonate-buffered solution, followed by one in which bicarbonate was replaced with imidazole (IPSS) to prevent precipitation of bicarbonate and CeCl3. Some hearts were made globally ischemic (30 min, 37 degrees C), reperfused 5 min with well-oxygenated IPSS containing 1 mM CeCl3, then processed for electron microscopy. Others were perfused with IPSS containing catalase (300 U/ml) or albumin before ischemia and upon reperfusion, followed by CeCl3 administration. Nonischemic control hearts perfused with IPSS (+/- catalase) were also studied. Electron micrographs were assessed visually and by computer for precipitate localization and amount. There was abundant precipitate on the luminal face of the coronary vascular endothelium in ischemic-reperfused, cerium-treated hearts, including those treated with albumin. There was significantly less in reperfused catalase-treated or nonischemic control hearts. X-ray microbeam analysis of the endothelial precipitate indicated the presence of Ce. This appears to be the first visual demonstration of a CeCl3-H2O2-dependent reaction product in intact isolated ischemic hearts. The data indicate that at the time of reperfusion some H2O2 is accessible to the vascular space, and that its amount can be reduced by perfused catalase. Further modifications this technique may be useful for assessing the sites and pathways by which H2O2 is generated by hearts or other buffer-perfused organs subjected to stresses such as ischemia or hypoxia.
J Mol Cell Cardiol 1990 Jan
PMID:Cerium chloride as a histochemical marker of hydrogen peroxide in reperfused ischemic hearts. 232 33

The membrane molecule termed "7F7-antigen" has been found to be involved in several examples of cell-cell interactions. This 85 kDa glycoprotein with a protein core of about 55 kDa contains N-linked and O-linked carbohydrates. It has an isoelectric point of 8.0-8.5 and is expressed on 20% of peripheral blood mononuclear cells, 35% of peripheral blood B-cells, follicular dendritic cells and vascular endothelium. It is also expressed on activated T-cells and its expression on B-cells, fibroblasts and monocytes increases after treatment with PWM, interferon-gamma and after three days culture, respectively. The MAb 7F7 used to define this antigen inhibits the initiation of T-cell proliferation induced by anti-CD3, PHA, ConA and (weakly) allogenic stimulator cells, but does not affect the growth of IL-2 dependent T-cells and does not interfere with the killing of PHA-blasts by allogenic IL-2 dependent T-cells. 7F7 also inhibits the binding of C3-coated sheep erythrocytes to B-cells, the PMA-induced aggregation of U937 and the binding of activated T-cells to fibroblasts. The 7F7-antigen is expressed on some non-Hodgkin lymphomas of B-cell differentiation, particularly those with follicular structure, but not on Burkitt's lymphoma, ALL or carcinomas of various tissues. It is, however, found on fibrous tissue surrounding infiltrating carcinoma cells. The expression of a melanoma antigen, P3.58, which was shown to be identical to 7F7-antigen correlates with stage and spread of invasive melanoma. It was concluded that the 7F7-antigen, which is probably related to a previously described adherence molecule (ICAM-1), is of biological importance for the initiation of T-cell responses. With the possible exception of melanoma its expression on neoplastic cells in vivo is unlikely to be of importance for the spread of malignant disease.
Mol Immunol 1988 Nov
PMID:Importance of an 85 kDa membrane glycoprotein for a variety of cell-cell interactions. 246 58

Ca2+-mobilizing receptor-induced inositol phospholipid hydrolysis has been studied in cultured endothelial cells (EC) from human aorta, pulmonary artery, and umbilical vein. It was shown that in EC the release of inositol phosphates can be stimulated by histamine, thrombin, serotonin, acetylcholine, carbachol, bradykinin, vasopressin, angiotensin II, platelet-activating factor (PAF), the thromboxane A2 mimetic, U46619, and prostaglandin E2. The most effective agonists were thrombin, histamine, and PAF, producing two- to five-fold increases in inositol phosphate level, and a 50-90% elevation of the level of inositol trisphosphate within 5 min. Effects of other agonists were smaller, although significant. Incubation of EC with histamine or PAF for 1 h resulted in a four- to eight-fold decrease of beta-adrenoreceptor density in the plasma membranes. The activity of isoproterenol-stimulated adenylate cyclase was depressed, and the degree of stimulation by isoproterenol was reduced. Similar effects were obtained after treatment of EC with the protein kinase C activator 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, suggesting a role of protein kinase C in receptor desensitization. It is concluded, that stimulation of inositol phospholipid hydrolysis, and, consequently, activation of protein kinase can cause receptor imbalance in human vascular endothelium. This mechanism may play a pivotal role in the pathogenesis of cardiovascular and pulmonary diseases.
J Mol Cell Cardiol 1989 Feb
PMID:Regulation of phosphoinositide turnover in endothelium from human pulmonary artery, aorta and umbilical vein. Antagonistic action on the beta-adrenoceptor coupled adenylate cyclase system. 254 21

Fatty acids, the preferred substrate in normoxic myocardium, are derived from either exogenous or endogenous triacylglycerols. The supply of exogenous fatty acids is dependent of the rate of lipolysis in adipose tissue and of the lipoprotein lipase activity at the coronary vascular endothelium. A large part of the liberated fatty acids is reesterified with glycerol-3-phosphate and converted to triacylglycerols. Endogenous lipolysis and lipogenesis are intracellular compartmentalized multienzyme processes of which individual hormone-sensitive steps have been demonstrated in adipose tissue. The triacylglycerol lipase is the rate-limiting enzyme of lipolysis and glycerol-3-phosphate acyltransferase and possibly phosphatidate phosphohydrolase are the rate-limiting enzymes of lipogenesis. The hormonal regulation of both processes in heart is still a matter of dispute. Triacylglycerol lipase activity in myocardial tissue has two intracellular sources: 1. the endoplasmic reticular and soluble neutral lipase, and 2. the lysosomal acid lipase. Studies in our laboratory have indicated that whereas lipolysis is enhanced during global ischemia and anoxia, overall lipolytic enzyme activities in heart homogenates were not altered. In addition we were unable to demonstrate alterations in tissue triacylglycerol content and glycerol-3-phosphate acyltransferase activity under these conditions. Lipolysis, is subject to feedback inhibition by product fatty acids. Therefore all processes leading to an increased removal of fatty acids from the catalytic site of the lipase will stimulate lipolysis. These studies will be reviewed. In addition, studies from our department have demonstrated the capacity of myocardial lysosomes to take up and degrade added triacylglycerol-particles in vitro. Such a process, stimulated by Ca2+ and stimulated by acidosis, offers another physiological target for hormone actions.
Mol Cell Biochem
PMID:Hormones and triacylglycerol metabolism under normoxic and ischemic conditions. 267 63

Interactions between platelets with injured vascular endothelium contribute to thrombotic occlusion. A murine monoclonal antibody [7E3 F(ab')2] to the platelet GPIIb/IIIa receptor complex was used to inhibit platelet aggregation in an experimental model of coronary artery thrombosis. Prevention of thrombotic occlusion by 7E3 F(ab')2 (0.8 mg/kg bolus i.v.) was studied in dogs with direct current induced intimal injury (100 microA for 5 h) and critical stenosis of the left circumflex coronary artery (LCCA). Baseline LCCA blood flow (CBF) was similar in 7E3 F(ab')2 and control groups, but decreased in the controls [24 +/- 2 ml/min to 0 +/- 0 ml/min, n = 13 (mean +/- S.E.M.)] due to thrombotic occlusion in each case (time to thrombosis 136 +/- 15 min). In the group treated with 7E3 F(ab')2, CBF did not change significantly (27 +/- 3 ml/min to 22 +/- 3 ml/min, n = 6) and thrombotic occlusion did not occur during the 5-h observation period in which intimal injury was produced in the LCCA (P less than 0.001). Oscillations in CBF preceded thrombosis in the control group, but did not occur with 7E3 F(ab')2 treatment (2.2 +/- 0.7 vs. 0 +/- 0, P less than 0.05). The thrombus mass recovered from the LCCA 30 min after occlusion was 8.8 +- 1.3 mg in the controls compared to 2.2 +/- 1.2 mg determined 5 h after administration of 7E3 F(ab')2 (P less than 0.05). When studied ex vivo, before the administration of the test agents, platelets from both groups of dogs aggregated in response to ADP and arachidonic acid. However, after treatment, the ex vivo aggregation of platelets from 7E3 F(ab')2 animals was inhibited whereas platelets from the control animals continued to aggregate ex vivo throughout the period of the experimental protocol (P less than 0.05). The labeling of platelets with 111indium showed accumulation of radioactivity within the thrombus and upon the vascular endothelium which was less in 7E3 F(ab')2 treated dogs as compared to the control group (P less than 0.05). The murine monoclonal antibody 7E3 F(ab')2 did not affect hemodynamic values or the circulating platelet count during the experimental protocol. In conclusion, antibody to platelet GPIIb/IIIa receptors: (1) prevented thrombotic LCCA occlusion, (2) inhibited ex vivo platelet aggregation, (3) minimized platelet deposition on injured vascular endothelium and within formed thrombi, and (4) stabilized CBF during 5 h of continuous direct current induced intimal injury of the LCCA.
J Mol Cell Cardiol 1989 Apr
PMID:Antiplatelet monoclonal F(ab')2 antibody directed against the platelet GPIIb/IIIa receptor complex prevents coronary artery thrombosis in the canine heart. 274 60

The effects of oxygen-derived radical scavengers (ODRS) on the heart was investigated during the calcium paradox. Perfusion with Ca2+-free medium caused cell separation at the intercalated discs and changes in the endothelial cells. Upon Ca2+ reintroduction, a massive cell damage occurred. The cytosolic enzyme, creatine phosphokinase (CPK), was released in large amounts (p less than 0.001). The tissue adenosine triphosphate (ATP) was reduced to 3.7 mumol/g dry weight from the control value of 21.6 mumol/g dry weight and tissue Ca2+ content was increased threefold. The treatment with superoxide dismutase (SOD) and catalase (CAT) increased percentage of normal cells (62.2%) compared to nontreated Ca2+ paradox group (0.2%) and caused negligible leakage of CPK. Tissue ATP was preserved (p less than 0.03), and Ca2+ content was also reduced in the hearts treated with SOD and CAT (p less than 0.03). The cell membranes and vascular endothelium were well preserved in the hearts treated with SOD and CAT. Boiled SOD and CAT administered were totally ineffective. It is suggested that oxygen-active species may have a role in the Ca2+ paradox injury.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Oxygen derived radicals related injury in the heart during calcium paradox. 289 1


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