scholarly journals Alcohol functionality in the fatty acid backbone of sphingomyelin guides the inhibition of blood coagulation

RSC Advances ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 3390-3398
Author(s):  
S. Mallik ◽  
R. Prasad ◽  
K. Das ◽  
P. Sen

Cell-surface sphingomyelin (SM) inhibits binary and ternary complex activity of blood coagulation.

1975 ◽  
Vol 18 (3) ◽  
pp. 347-356
Author(s):  
A.S. Curtis ◽  
J. Campbell ◽  
F.M. Shaw

Aggregation-inhibiting protein (AIP: Curtis & Greaves, 1965), which diminishes the adhesiveness of cells, particularly at low temperatures, is identified in the present paper as phospholipase A2 (EC. 3.1.1.4). Our reasons for this identification are because phospholipase activity parallels AIP activity on cell adhesion, and because various inhibitors and sera act in a parallel manner on adhesion in the presence of AIP or phospholipase. We suggest that the enzyme acts on adhesion by producing lysolecithin and other lysolipids in the plasmalemma. Addition of lysolipids diminishes cell adhesion in a manner similar to phospholipase A. Incubation of cells in Hanks' medium at 37 degrees C has a parallel effect. Conditions which would be expected to stimulate reacylation of lysolipids in the plasmalemma, i.e. incubation of cells in the external presence of CoA, ATP and a fatty acid, lead to a recovery or maintenance of adhesion after or during Hanks' incubation at 37 degrees C. All these results suggest that lipid components of the cell, probably in the plasmalemma, are of importance in adhesion. The results are discussed in relation to the long-standing controversy about the effects of low temperatures and trypsinization on cell adhesion, for phospholipase treatment of cells affects adhesion in a manner similar to trypsinization.


1981 ◽  
Author(s):  
J Schrader ◽  
H Köstering ◽  
H Kaiser ◽  
P Kramer ◽  
F Scheler

The blood coagulation system makes a significant contribution to renal damage in many disease processes. Intrarenal coagulation appears to occur in a wide variety of diseases as a primary or secondary event. As there is evidence that intraglomerular coagulation is a significant factor in the development and maintenance of oliguria in acute ischemic renal failure, blood coagulation investigations were performed in 20 patients with acute renal failure of varied etiology. The investigations were done on a daily basis from the onset of oliguria (urine flow <20 ml/h)until serum creatinine declined to less than 2,0 mg%. Thus, we were able to detect changes in blood coagulation during oliguria and polyuria. We found an enhanced thrombin generation in both oliguria and polyria. Fibrin monomer complexes were significantly increased in both states, but more predominantly in polyuria. Factor VIII and alpha-1 antitrypsin activities were also elevated. PTT and r- and k-time in TEG were shortened more in polyuria than in oliguria, whereas fibrinogen was elevated more in oliguria than in polyuria. Factor XIII activity and prothrombin complex activity (Quick’s test) were lowered in both states, the lowest values of the former being found in polyuria, the lowest values of the latter in oliguria with a normalizing tendency in the following days. Fibrinolytic activity was also decreased. No significant changes were found in plasminogen, antithrombin III, alpha-2 macroglobulin, factor V and thrombin time. In summary, we found a hypercoagulability in these patients with acute renal failure, which was more predominant during polyuria and which correlated with the tendency to thrombosis and to shorter indwelling periods of i.v. catheters in this state. Consequently, the changes in blood coagulation of 3 patients with acute postrenal failure were not as significant as those found in the other patients. The treatment with anticoagulants in patients with acute renal failure will be discussed.


2005 ◽  
Vol 94 (11) ◽  
pp. 1084-1093 ◽  
Author(s):  
Ingo Banke ◽  
Matthias Arlt ◽  
Markus Mueller ◽  
Stefan Sperl ◽  
Axel Stemberger ◽  
...  

SummaryClinical and experimental evidence suggests that the blood coagulation system is involved in the dissemination of malignant tumors. Consequently, anticoagulant agents have been tested as metastasis suppressors in experimental models. Recently, we have found a close correlation between factor Xa (FXa)-specificity of a series of synthetic serine protease inhibitors and their anti-metastatic potential in a murineT-cell lymphoma metastasis model. Interference of such inhibitors with blood-coagulation may represent a major experimental and clinical obstacle. Here, we test anti-metastatic effects of a recently developed, highly specific 3-amidinophenylalanine-type FXa inhibitor, WX-FX4, with weaker anticoagulant activity when compared to well-established FXa inhibitors, such as DX-9065a, as measured by the activated partial thromboplastin time, prothrombin time, prothrombinase complex activity, and coagulation time. Treatment of mice with WX-FX4 (1.5 mg/kg twice daily) led to significant reduction of experimental liver metastasis of a syngeneic T-cell lymphoma in DBA/2 mice (> 90%), and of experimental lung metastasis of a human fibrosarcoma in CD1 nu/nu mice (> 60%). Due to its relatively low anticoagulant activity, daily treatment over 100 days was possible, leading to significant survival benefits without inducing bleeding anomalities. FXa-inhibitors with highly efficient anti-metastatic potential without coagulationrelated side effects may represent important new tools as anticancer agents.


2009 ◽  
Vol 296 (4) ◽  
pp. H1108-H1116 ◽  
Author(s):  
Fang Wang ◽  
Min Suk Kim ◽  
Prasanth Puthanveetil ◽  
Girish Kewalramani ◽  
Sylvia Deppe ◽  
...  

Following diabetes, the heart increases its lipoprotein lipase (LPL) at the coronary lumen by transferring LPL from the cardiomyocyte to the endothelial lumen. We examined how hyperglycemia controls secretion of heparanase, the enzyme that cleaves myocyte heparan sulphate proteoglycan to initiate this movement. Diazoxide (DZ) was used to decrease serum insulin and generate hyperglycemia. A modified Langendorff technique was used to separate coronary from interstitial effluent, which were assayed for heparanase and LPL. Within 30 min of DZ, interstitial heparanase increased, an effect that closely mirrored an augmentation in interstitial LPL. Endothelial cells were incubated with palmitic acid (PA) or glucose, and heparanase secretion was determined. PA increased intracellular heparanase, with no effect on secretion of this enzyme. Unlike PA, glucose dose-dependently lowered endothelial intracellular heparanase, which was strongly associated with increased heparanase activity in the incubation medium. Preincubation with cytochalasin D or nocodazole prevented the high glucose-induced depletion of intracellular heparanase. Our data suggest that following hyperglycemia, translocation of LPL from the cardiomyocyte cell surface to the apical side of endothelial cells is dependent on the ability of the fatty acid to increase endothelial intracellular heparanase followed by rapid secretion of this enzyme by glucose, which requires an intact microtubule and actin cytoskeleton.


1994 ◽  
Vol 267 (5) ◽  
pp. H1862-H1871 ◽  
Author(s):  
R. L. Collins-Nakai ◽  
D. Noseworthy ◽  
G. D. Lopaschuk

Although epinephrine is widely used clinically, its effect on myocardial energy substrate preference in the intact heart has yet to be clearly defined. We determined the effects of epinephrine on glucose and fatty acid metabolism in isolated working rat hearts perfused with 11 mM glucose, 0.4 mM palmitate, and 100 muU/ml insulin at an 11.5-mmHg left atrial preload and a 60-mmHg aortic afterload. Glycolysis and glucose oxidation were measured in hearts perfused with [5–3H]glucose and [U-14C]glucose, whereas fatty acid oxidation was measured in hearts perfused with [1–14C]palmitate. Addition of 1 microM epinephrine resulted in a 53% increase in the heart rate-developed pressure product. Glycolysis increased dramatically following addition of epinephrine (a 272% increase), as did glucose oxidation (a 410% increase). In contrast, fatty acid oxidation increased by only 10%. Epinephrine treatment did not increase the amount of oxygen required to produce an equivalent amount of ATP; however, epinephrine did increase the uncoupling between glycolysis and glucose oxidation in these fatty acid-perfused hearts, resulting in a significant increase in H+ production from glucose metabolism. Overall ATP production in epinephrine-treated hearts increased 59%. The contribution of glucose (glycolysis and glucose oxidation) to ATP production increased from 13 to 36%, which was accompanied by a reciprocal decrease in the contribution of fatty acid oxidation to ATP production from 83 to 63%. The increase in glucose oxidation was accompanied by a significant increase in pyruvate dehydrogenase complex activity in the active form. We conclude that the increase in ATP required for contractile function following epinephrine treatment occurs through a preferential increase in glucose use.


2002 ◽  
Vol 68 (11) ◽  
pp. 5258-5264 ◽  
Author(s):  
Monica S. To ◽  
Stacy Favrin ◽  
Nadya Romanova ◽  
Mansel W. Griffiths

ABSTRACT Many studies have demonstrated that bacteria, including Listeria monocytogenes, are capable of adapting to disinfectants used in industrial settings after prolonged exposure to sublethal concentrations. However, the consequent alterations of the cell surface due to sanitizer adaptation of this pathogen are not fully understood. Two resistant and four sensitive L. monocytogenes strains from different sources were progressively subcultured with increasing sublethal concentrations of a surfactant, benzalkonium chloride (BC). To evaluate the effects of acquired tolerance to BC, parent and adapted strains were compared by using several morphological and physiological tests. Sensitive strains showed at least a fivefold increase in the MIC, while the MIC doubled for resistant strains after the adaptation period. The hydrophobicities of cells of parent and adapted strains were similar. Serological testing indicated that antigen types 1 and 4 were both present on the cell surface of adapted cells. The data suggest that efflux pumps are the major mechanism of adaptation in sensitive strains and are less important in originally resistant isolates. A different, unknown mechanism was responsible for the original tolerance of resistant isolates. In an originally resistant strain, there was a slight shift in the fatty acid profile after adaptation, whereas sensitive strains had similar profiles. Electron micrographs revealed morphological differences after adaptation. The changes in cell surface antigens, efflux pump utilization, and fatty acid profiles suggest that different mechanisms are used by resistant and sensitive strains for adaptation to BC.


Extremophiles ◽  
2000 ◽  
Vol 4 (5) ◽  
pp. 285-290 ◽  
Author(s):  
I. Yumoto ◽  
Koji Yamazaki ◽  
Megumi Hishinuma ◽  
Yoshinobu Nodasaka ◽  
Norio Inoue ◽  
...  

2008 ◽  
Vol 52 (10) ◽  
pp. 3669-3680 ◽  
Author(s):  
Anil K. Mangalappalli-Illathu ◽  
Sinisa Vidović ◽  
Darren R. Korber

ABSTRACT This study examined the adaptive response and survival of planktonic and biofilm phenotypes of Salmonella enterica serovar Enteritidis adapted to benzalkonium chloride (BC). Planktonic cells and biofilms were continuously exposed to 1 μg ml−1 of BC for 144 h. The proportion of BC-adapted biofilm cells able to survive a lethal BC treatment (30 μg ml−1) was significantly higher (4.6-fold) than that of BC-adapted planktonic cells. Similarly, there were 18.3-fold more survivors among the BC-adapted biofilm cells than among their nonadapted (i.e., without prior BC exposure) cell counterparts at the lethal BC concentration, and this value was significantly higher than the value for BC-adapted planktonic cells versus nonadapted cells (3.2-fold). A significantly higher (P < 0.05) proportion of surviving cells was noticed among BC-adapted biofilm cells relative to BC-adapted planktonic cells following a 10-min heat shock at 55°C. Fatty acid composition was significantly influenced by phenotype (planktonic cells or biofilm) and BC adaptation. Cell surface roughness of biofilm cells was also significantly greater (P < 0.05) than that of planktonic cells. Key proteins upregulated in BC-adapted planktonic and biofilm cells included CspA, TrxA, Tsf, YjgF, and a probable peroxidase, STY0440. Nine and 17 unique proteins were upregulated in BC-adapted planktonic and biofilm cells, respectively. These results suggest that enhanced biofilm-specific upregulation of 17 unique proteins, along with the increased expression of CspA, TrxA, Tsf, YjgF, and a probable peroxidase, phenotype-specific alterations in cell surface roughness, and a shift in fatty acid composition conferred enhanced survival to the BC-adapted biofilm cell population relative to their BC-adapted planktonic cell counterparts.


1963 ◽  
Vol 10 (01) ◽  
pp. 164-189 ◽  
Author(s):  
M. J Silver ◽  
D. L Turner ◽  
I Rodalewicz ◽  
N Giordano ◽  
R Holburn ◽  
...  

Summary1. The effects of phospholipids, solubilized by different methods in different clotting tests are presented.2. Complete fatty acid analysis of a phosphatidylserine fraction from beef brain is given.3. Data relating electric charge of phospholipid particles to activity in clotting are presented.4. A critical discussion of the factors which influence the activity of phospholipids in blood clotting terminates the paper.


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