Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin E is a fat-soluble antioxidant which plays an important role in maintaining cells in a reduced state. Oxidation reactions can lead to damage of both endothelial cells and circulating blood cells and may thus influence the rheological conditions. A group of 13 mountaineers was selected as a model for persons at increased risk of oxidative stress. 6 subjects received 200 mg vitamin E twice daily for 4 weeks, and 7 subjects received placebo. Erythrocyte filterability, blood viscosity, changes in the blood picture, and three blood coagulation factors (antithrombin III, protein C, and fibrin monomers) were investigated. The baseline values (t1) were determined at 1.500 m, and after supplementation the investigations were repeated twice at 4.300 m (t2 und t3). There was a marked rise in the hematocrit in both groups during the ascent which was due to an increase not only of the erythrocytes but also of the leucocytes. This change was more pronounced in the control group. The erythrocyte filterability was unaltered in the vitamin E group in comparison with baseline but was significantly impaired in the control group. The changes in these two parameters-hematocrit and filterability--resulted in a significant higher blood viscosity. Furthermore in the control group, but not in the vitamin E group, a significant fall in the protein C activity was observed. The cause may be an additional release from degenerated leucocytes of various proteases which degrade protein C. A further possible cause is a derangement of metabolic reactions in the vascular endothelium. All these possible causes could be counteracted by the higher antioxidative potential of the verum group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of vitamin E on rheological parameters in high altitude mountaineers. 238 67

Over a period of 7 years a typical hemolytic uremic syndrome (HUS) developed in 3 brothers, at the age of 27, 31 and 35 years respectively. The patients did not share a common HLA haplotype. Two sisters, now 36 and 39 years old, did not develop HUS despite pregnancy and prolonged oral contraception. We investigated in the 3 patients (outside of the acute phase of the HUS) and in 12 other first degree relatives complement components (C3, C4, C1q, factor B), coagulation factors (i.e., antithrombin III, F VIII, protein C) prostacyclin regulating plasma factor and vitamin E levels: all results were normal. Renal failure was irreversible in the 3 patients, despite fresh plasma infusions in 2 of them. After a 7 to 32-month period on hemodialysis, the 3 patients were transplanted with a cadaver kidney. Twenty-one to 94 months later, they have a functioning graft and no recurrence of the HUS. We conclude that, in this family, HUS is not linked to HLA or female gender. No phenotypic marker of the disease was found. Evolution after dialysis and transplantation is excellent, with no short term recurrence of the HUS.
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PMID:Hemolytic uremic syndrome in three adult siblings: a familial study and evolution. 348 Jul 83

The aim of the present study was to investigate whether the overall oxidation state of plasma proteins is associated with changes of circulating pro- and anticoagulant markers in healthy subjects (n = 99, 49 males, 50 females, aged from 6 to 91 yrs.). The carbonyl content of plasma proteins was measured and validated as an ex vivo index of the overall protein oxidation state due to its correlation with the plasma level of o-tyrosine (r = 0.87, P <0.0001), which is a well known oxidized product of L-phenylalanine. Using a multivariate analysis the carbonyl content of plasma protein was positively associated with procoagulant markers such as prothrombin F1 + 2 (r = 0.28, P = 0.0019) and fibrinopeptide A, (FpA) (r = 0.278, P = 0.003), as well as with the soluble derivative of the endothelial protein thrombomodulin (TM) (r = 0.469, P <0.0001). The procoagulant marker of thrombin activity, FpA, was significantly and positively correlated with the anticoagulant product of thrombin, namely the Protein C activation peptide (PCP), only in the tertile with low protein carbonyl content. At higher tertiles this correlation was no longer observed, thus suggesting a detrimental effect of oxidative stress on the TM/Protein C anticoagulant pathway. In 15 subjects with high carbonyl content of plasma protein, treatment for 18 days with 600 mg/d of vitamin E did not substantially modify the protein carbonyl content, the anticoagulant markers APC/PCP, and all procoagulant markers except F1+2, whose value significantly decreased by 25%. In conclusion, the present study shows that a high plasma protein oxidation ex vivo is associated with an overall hemostatic imbalance, which favors procoagulant markers. Vitamin E treatment in vivo restores only in part the equilibrium between pro- and anticoagulant pathways. This may open the way to further studies aimed at elucidating the mechanisms by which the oxidative stress is linked to activation of the coagulation system in atherothrombotic disorders.
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PMID:Plasma protein oxidation is associated with an increase of procoagulant markers causing an imbalance between pro- and anticoagulant pathways in healthy subjects. 1184 57

Aging is associated with reduced IL-2 production and T cell proliferation. Vitamin E supplementation, in aged animals and humans, increases cell division and IL-2 production by naive T cells. The immune synapse forms at the site of contact between a T cell and an APC and participates in T cell activation. We evaluated whether vitamin E affects the redistribution of signaling proteins to the immune synapse. Purified CD4(+) T cells, from the spleens of young and old mice, were treated with vitamin E before stimulation with a surrogate APC expressing anti-CD3. Using confocal fluorescent microscopy, we observed that CD4(+) T cells from old mice were significantly less likely to recruit signaling proteins to the immune synapse than cells from young mice. Vitamin E increased the percentage of old CD4(+) T cells capable of forming an effective immune synapse. Similar results were found following in vivo supplementation with vitamin E. When compared with memory cells, naive T cells from aged mice were more defective in immune synapse formation and were more responsive to vitamin E supplementation. These data show, for the first time, that vitamin E significantly improves age-related early T cell signaling events in naive CD4(+) T cells.
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PMID:Age-associated decline in effective immune synapse formation of CD4(+) T cells is reversed by vitamin E supplementation. 1723 92

Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR) and strongly induce endothelial thrombomodulin (TM); which is known to have anti-inflammatory; anti-coagulation; anti-oxidant; and radioprotective properties. However; high-dose toxicity limits the clinical use of statins. The vitamin E family member gamma-tocotrienol (GT3) also suppresses HMGCR activity and induces TM expression without causing significant adverse side effects; even at high concentrations. To investigate the synergistic effect of statins and GT3 on TM; a low dose of atorvastatin and GT3 was used to treat human primary endothelial cells. Protein-level TM expression was measured by flow cytometry. TM functional activity was determined by activated protein C (APC) generation assay. Expression of Kruppel-like factor 2 (KLF2), one of the key transcription factors of TM, was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). TM expression increased in a dose-dependent manner after both atorvastatin and GT3 treatment. A combined treatment of a low-dose of atorvastatin and GT3 synergistically up-regulated TM expression and functional activity. Finally; atorvastatin and GT3 synergistically increased KLF2 expression. These findings suggest that combined treatment of statins with GT3 may provide significant health benefits in treating a number of pathophysiological conditions; including inflammatory and cardiovascular diseases.
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PMID:The Vitamin E Analog Gamma-Tocotrienol (GT3) and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM). 2786 47