1,721,069 research outputs found
CoA Protects VLDL Against Peroxidation and Increases the Plasma Triacylglycerol Metabolism
CoA (coenzyme A) has an antiperoxidative action and protects erythrocytes against oxygen free radicals. The peroxidation favours the uptake of the modified LDL (low-density lipoprotein) by macrophages and has a role in the development of foam cells. A possible relation between the antiperoxidative action of CoA and its normalizing activity on plasma lipids in type IIb and type IV hyperlipoproteinaemias, was investigated in order to see whether CoA protects VLDL (very -low-density lipoproteins) against peroxidation and produces a quicker removal of VLDL from circulation when administered intravenously to rats. The addition of 5 mM CoA to rat hepatocytes in culture was found to produce a significant decrease in VLDL secretion. The plasma clearance was significantly more rapid and the removal of triacylglycerols was significantly enhanced in CoA-treated rats as compared to untreated ones. Furthermore CoA reduced the formation of material reacting with thiobarbituric acid (TBA) in human VLDL peroxidized by exposure to Cu2+. Our study shows that CoA protects VLDL from peroxidation in a significant and concentration-dependent manner and increases plasma triacylglycerol metabolism
Physiologic pH changes modulate calcium ion dependence of brain nitric oxide synthase in Carassius auratus
Species of the fish genus Carassius survive prolonged anoxia. Nitric oxide (NO) regulates cerebral blood flow in these fish during normoxic conditions whereas adenosine is the main vasoregulating molecule during anoxia. We investigated the calcium ion dependence of Carassius auratus brain NO synthase (NOS) as a function of pH. The physiological pH decrease from 7.2 to 6.8, which takes place during anoxia, greatly decreases NOS activity. This strong pH dependence is mainly due to variation of the calcium sensitivity of the enzyme. The EC50 is 0.15 muM at pH 7.2 and 2.1 muM at pH 6.8 for the soluble enzyme. The particulate enzyme is also dependent on pH variations. The reduced sensitivity to calcium ions at acidic pH decreases both NO and H2O2 production, saving the cells by suppression of the formation of potentially toxic nitrogen and oxygen species. Modulation of NOS activity by variation of its calcium affinity within the range of physiological pH constitutes an important and rapid mechanism to control the formation of NO and H2O2 during normoxia-anoxia and anoxia-normoxia transitions. (C) 2002 Elsevier Science B.V. All fights reserved
Role of pH on the calcium ion dependence of the nitric oxide synthase in the carp brain
The role of pH on the calcium dependence of nitric oxide synthase (NOS) of Cyprinus carpio brain was investigated. This fish is known to survive prolonged periods of hypoxia. Under this condition, cerebral blood flow is no longer regulated by nitric oxide (NO). Nitric oxide synthase activity is pH dependent in the range of pH between 7.4 and 6.2 with a decrease when tissue acidifies. At acidic pH, the dependence of the NOS activity on the free Ca2+ concentrations changes considerably and shows an EC50 of 0.13 muM at pH 7.1 and of 5.1 muM at pH 6.2 for the soluble enzyme. The variation in the Ca2+ dependence with acidification is greater for the soluble than for the particulate enzyme. This may be the main factor protecting sudden NO formation mainly during anoxic-normoxic transitions
Calcium/calmodulin dependence of nitric oxide synthase from Viviparus aeter immunocytes
The calcium ion dependence of soluble and particulate NOS activity from Viviparus ater hemocytes has been investigated. At 2 nM calcium ion concentration the NOS activity measured by citrulline formation is 27.1 ± 2.2 and 9.3 ± 0.8 pmol.min-1.106cell-1 for soluble and particulate NOS respectively. The increase of free calcium ion concentration up to 300 nM increases the enzyme activity to 57.5 ± 4.1 and 23.5 ± 1.2 respectively. The 50% activation of the calcium dependent activity is 91 and 97 nM Ca2+ for soluble and particulate enzyme. Trifluoperazine, an inhibitor of calmodulin dependent enzyme, partially inhibits both activities. The soluble NOS is five time more sensible than particulate NOS. The behaviour of both activities to three NOS inhibitors (7-nitroindazole, S-methylisothiourea sulfate, diphenyleneiodonium) is very similar with not significant differences in IC50 values. The calcium ion dependence of NOS activities in a range of free calcium ion variations which are transiently observed in receptor stimulated cells suggests that NO in V. ater hemocytes has not only a defensive role but also a signalling relevance in cross-talking between hemocytes and other cells
Metabolic Fate of Partially Depolymerized Shark Chondroitin Sulfate in Man
Chondroitin sulfates and other glycosaminoglycans are administered as drugs to man by intravenous, intramuscular or oral routes. There are some studies on the pharmacokinetics of heparin, heparan sulfate and dermatan sulfate, whereas few data are available on the metabolic fate of chondroitin sulfate in man. Partially depolymerized chondroitin sulfate (mean mol. wt: 7.5 kd, range 5-10 kd) with a ratio of 1:3 between chondroitin-4-sulfate and chondroitin-6-sulfate has been administered as single administrations of 0.2 and 1.2 g by intramuscular and oral routes respectively to 10 healthy volunteers (5 males and 5 females), aging 25-53 years. After intramuscular administration the plasma level increased to a concentration peak at 90 min. The peak concentration, the elimination half-life and the apparent distribution volume were respectively 3.8 mcg/ml, 275 min and 0.40 ml/g. About 37% of the administered chondroitin sulfate is excreted in the urine during the first 24 h as high- and low-molecular-weight derivatives. After oral administration the concentration peak was observed at 240 min. The concentration at the peak, the elimination half-life and the apparent distribution volume were respectively 4.6 mcg/ml, 310 min and 0.44 ml/g. A peak of mono-, oligo- and polysaccharides with a molecular weight lower than 5 kd derived from partial digestion of exogenous chondroitin sulfate is also present in plasma. This study shows that about 10% and 20% of the orally administered drug is absorbed as high- and low-molecular-weight derivatives respectively. Comparison with the results obtained in experimental animals indicate that the metabolic fate of partially depolymerized chondroitin sulfate is similar in man and in experimental animals
Metabolizzazione della 4-Carbometossitiazolidina Cloridrato a Cisteina ad Opera di Espettorati ed Omogenati di Polmone Umani e sua Azione sulle Glicoproteine del Muco
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From balsamic to healthy: traditional balsamic vinegar melanoidins inhibit lipid peroxidation during simulated gastric digestion of meat
In this work traditional balsamic vinegar (TBV) melanoidins were characterized for chemical composition and antioxidant activity and their antiperoxidative effect during an in vitro gastric digestion of turkey meat was studied. The most important constituents of TBV melanoidins were carbohydrates (51% w/w) of which glucose (35% w/w) and fructose (10% w/w) are the main representatives, hydroxymethylfurfural (HMF) (7.2% w/w), phenolic groups (4.6% w/w) and proteins (1.2% w/w). The antioxidant capacity of melanoidins was studied, measuring lipid hydroperoxides and secondary lipoxidation products formed during in vitro gastric digestion of turkey meat. The most important mechanisms in their antioxidant activity resulted radical scavenging and Fe2+-chelating activities. Pepsin inhibiting ability has been excluded.. TBV melanoidins were also able to bind heme under gastric conditions potentially preventing its absorption and prooxidant and cytotoxic effects. Our results support the idea that TBV melanoidins may have a role in oxidative damage prevention. Fe2+-chelating and heme-binding activities as well as mechanisms of antioxidant activity of TBV melanoidins were also compared with coffee, barley coffee and dark beer melanoidins
Recent Findings on the Regulatory Function of CoA and on the Normalizing Activity on Plasma Lipids of Exogenous CoA
In recent years many studies have shown that coenzyme A (CoA) is not only an acyl carrier coenzyme but it also has an important role in the regulation of metabolic functions and cell activities such as transport from the Golgi cisternae. This regulatory role is carried out by CoA, its precursor, catabolites and acylated derivatives. The acylation (myristylation and palmitylation) process of peptides and proteins dependent on CoA seems to be an important regulatory mechanism of cell activities. Furthermore exogenous CoA has been shown to decrease the triacylglycerols, cholesterol and Apo B of plasma lipoproteins in man. This regulatory mechanism acts either on VLDL synthesis and secretion or on their plasma clearance. CoA also protects cell-membrane and plasma lipoproteins against the peroxidative action of oxygen free-radicals
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