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O A Azizova

Publications and source records attributed to O A Azizova.

At least 37 records · Page 2Linked to original sources
PubMed1997

Inhibitor analysis of LDL-induced platelet aggregation.

Oxidized low density lipoproteins (oxLDL) bounded to specific receptors on the platelet surface are able to activate platelets. However, the exact mechanism of signal transduction from LDL receptors into the cell still requires investigation. In the present paper inhibitors of the main enzymes of known platelet activation pathways were used to investigate the mechanism of the LDL-induced platelet aggregation. Our experiments were performed with autoxidized LDL (2-thiobarbituric acid reactive substances < 8 nmoles/mg). We demonstrated that the main enzymes of the arachidonate cycle do not play an important role in LDL-induced platelet aggregation, whereas inhibition of protein kinase C and phospholipase C--principal enzymes of the phosphoinositide cycle--resulted in the inhibition of LDL-induced platelet aggregation in a dose-dependent manner. It was also shown that transmembrane calcium transport was necessary for LDL-induced platelet activation. Thus, we conclude that the phosphoinositide cycle is the main mechanism of cellular signal transduction during LDL-induced platelet activation.

Acetophenones↗
PubMed1993

Simultaneous determination of Fe(III) and Fe(II) in water solutions and tissue homogenates using desferal and 1,10-phenanthroline.

At neutral pH values 1,10-phenanthroline forms a colored complex with Fe(II), but it does not form such a complex with Fe(III). On the contrary, only Fe(III) forms with desferal a yellow complex with a g = 4.3 electron paramagnetic resonance (EPR) signal, but Fe(II) is rapidly oxidized by desferal to Fe(III), which gives then a yellow complex. On the basis of these facts, a method for simultaneous determination of both Fe(II) and Fe(III) ions was elaborated using a desferal-phenanthroline mixture. Two ways of detecting Fe(II) and Fe(III) have been suggested: (1) the spectrophotometric method for transparent water solutions, and (2) the EPR-spectrometric method for turbid solutions and tissue homogenates. The latter method was applied for determination of free and weakly bound iron in rat liver. The Fe(II) amount in intact liver was 22.2 +/- 7.6 nmol/g of wet tissue; free Fe(III) was not found.

Animals↗
PubMed1993

[The effect of lipid peroxidation-modified lipoproteins on thrombocyte aggregation].

Platelet aggregation induced by native and oxidized low-density lipoproteins (LDL) was studied. The minimal LDL concentration necessary for platelet activation was no more than 0.2 mg/ml. The aggregation rate increased when LDL concentration rose from 0 to 0.4-0.6 mg/ml for native LDL and to 0.2-0.4 mg/ml for oxidized LDL. The platelet aggregation induced by oxidized LDL appeared to be higher than that induced by the same concentration of native LDL. The dependence of aggregation rate on the degree of LDL peroxidation was linear up to MDA concentration equal to 3-4 mg/ml. Further LDL peroxidation leads only to the negligible increase in the induced aggregation rate.

Adenosine Diphosphate↗
PubMed1993

Influence of polar polymers on the apoprotein region of human serum lipoproteins: an electron paramagnetic resonance (EPR) study.

Electron spin resonance spectroscopy was used for measurements of the surface potential and apoprotein structure of LDL and HDL in the presence of Ca2+ and dextran sulfate, heparin and chondroitin sulfate. A decrease in the absolute values of surface potential of LDL and HDL was observed after addition of Ca2+. In the presence of the negatively charged macromolecules the measured surface potential was less reduced. The spectral properties of a maleimide spin label covalently attached to the apoprotein were changed under conditions of aggregation of LDL induced by dextran sulfate, chondroitin sulfate or heparin in the presence of Ca2+. In the HDL system this effect was only observed for dextran sulfate. The influence of PEG on the spectral parameters of the spin label is dependent on the molecular weight of the polymer. PEG 400 decreased the mobility of the spin-labelled apoprotein region of LDL, whereas PEGs with higher molecular weight only slightly increased the maleimide mobility. On the other hand, the maleimide-labelled apoprotein region of HDL showed a higher sensibility to all PEGs used. Addition of PEG leads to immobilization of apoprotein A.

Apolipoproteins↗
PubMed1992

Surface potential changes of mitoplasts in the presence of pyridoxal phosphate modified cytochromes c.

1. The addition of native cytochrome c to mitoplasts leads to a decrease of surface potential of the mitoplast membrane. However the surface potential is slightly decreased (approximately 3 mV) when PLP(Lys 86)-cytochrome c and PLP(Lys 79)-cytochrome c were added. 2. The native and PLP-modified cytochromes c do not influence the order parameters S and isotropic constant a when both spin probe I and probe II were used. It is shown that cytochrome c binding to the membrane does not affect the hydrophobic intermembrane area as well as the lipid arrangements of the mitoplast membrane. 3. At low ionic strength there was observed a significant difference in the membrane potential when PLP-cytochromes c were added to the mitoplasts. 4. At high ionic strength the addition of native or PLP-modified cytochromes c does not change the membrane potential.

Cytochrome c Group↗
PubMed1992

Intracellular free iron in liver tissue and liver homogenate: studies with electron paramagnetic resonance on the formation of paramagnetic complexes with desferal and nitric oxide.

Treatment of intact liver and liver homogenate with sodium nitrite, or desferal, brings about the appearance of g = 2.03 and g = 4.3 electron paramagnetic resonance spectroscopy (EPR) signals, respectively. The g = 2.03 signal is conditioned by the formation of dinitrosyl complexes of Fe(II); the g = 4.3 signal is related to the appearance of paramagnetic desferal-Fe(III) complexes. Desferal and sodium nitrite were administered successively into liver homogenate, resulting in only a g = 4.3 EPR signal. And, vice versa, if desferal was administered after sodium nitrite, there appeared only the signal with g = 2.03. These data testify to the fact that one and the same endogenous free iron is included in both paramagnetic centers. The concentration of iron ions was measured in intact tissue according to the formation of dinitrosyl-iron complexes and desferal-iron complexes. It was 33.2 +/- 4.6 and 20.3 +/- 4.0 nmol/g of tissue weight, respectively. The data obtained testify to the fact that free endogenous iron is present in intact tissue. Possibilities of the EPR method for estimation of the content of intracellular free iron are discussed.

Animals↗
PubMed1991

Free radical modification of lipoproteins and cholesterol accumulation in cells upon atherosclerosis.

An electron spin probe study was made of the effect of lipid peroxidation (LPO) on the structure of surface proteolipid layer of human serum low-density lipoproteins (LDL). The results obtained with a positively charged spin label and stearic acid spin probes with doxyl labels at positions 5, 12, and 16 revealed that LPO caused a decrease in phospholipid molecule mobility both in the region of polar heads and in the region of acyl chains till the depth of at least 1.7 mm from water-lipid interface. Under relatively high levels of oxidation (more than 6 mumol MDA/g LDL phospholipid) the polarity of lipid phase increased. The decrease in efficiency of tryptophan fluorescence quenching by nitroxide fragments incorporated in hydrophobic regions at the depth of approximately 2 nm from water-lipid interface indicated that lipid-protein interaction was disturbed as a result of oxidation of LDL lipids. In addition, the LPO-induced modification of apo-B, the main protein of LDL, was examined with maleimide spin label. LPO led to increase in mobility of strongly immobilized maleimide labels and in the number of weakly immobilized ones. Oxidized LDL revealed decreased ability to incorporate spin-labeled steroid (androstane) as compared to native ones. LPO-induced structural changes of LDL surface are supposed to be a reason of enhanced accumulation of cholesterol in human monocytes during their incubation with oxidized LDL. The cholesterol content in red cells was shown to be directly correlated to MDA content in apo-B containing lipoproteins but not in whole serum. Our findings suggest that free radical modification of serum lipoproteins but not solely an increased level of LPO products in blood is one important cause for cholesterol accumulation in cells and, apparently, for their transformation into foam cells during atherosclerosis.

Arteriosclerosis↗
PubMed1991

Antioxidant properties of albumin during the oxidation of linolenic acid and low density lipoproteins in the presence of ferrous ions.

A spin-labelled fatty acid with an epr spectrum that is sensitive to the localization of the probe was used to show that albumin binds free fatty acids present in solution and also free fatty acids present in low density lipoproteins (LDL). Furthermore, albumin binds the thiobarbituric acid-reactive (TBA-reactive) products formed during the oxidation of linolenic acid, whereas the TBA-reactive substances formed during the oxidation of LDL are not bound by albumin. Linolenic acid bound to albumin essentially does not undergo peroxidation in the presence of ferrous ions, in contrast to a suspension of linolenic acid and LDL in which peroxidation occurs quite readily in the presence of ferrous ions. The highest rate of oxidation was found for linolenic acid alone. Albumin-bound spin-labelled fatty acid was essentially not reduced by ferrous ions, whereas free fatty acid or fatty acid incorporated into LDL was reduced quite rapidly, the highest rate of reduction being for free fatty acids. Thus the ability of fatty acids to undergo oxidation correlates with their accessibility to ferrous ions. The data obtained indicate that serum albumin is a relatively effective antioxidant in the blood and its mode of action is based on the immobilization of free fatty acids.

Animals↗
PubMed1991

Free-radical generation by monocytes and neutrophils: a possible cause of plasma lipoprotein modification.

The activation of freshly isolated human blood monocytes and neutrophils monitored by oxidized human plasma lipoproteins (LP) was measured by detecting luminol-amplified chemiluminescence. The activation was accompanied by production of superoxide radicals. This finding was confirmed by measuring superoxide dismutase-sensitive reduction of cytochrome c. Incubation of monocytes or neutrophils with low-density lipoproteins (LDL) resulted in the accumulation of lipid peroxidation (LPO) products which were assayed by the 2-thiobarbituric acid test. Data from inhibitory analysis suggest that the hydroxyl radical scavenger, mannitol, had no appreciable effect on the accumulation of LPO products during the incubation of LDL with either cell type. However, catalase, superoxide dismutase, the metal ion chelators desferrioxamine and EDTA, as well as the free radical scavenger, butylated hydroxytoluene, markedly decreased the accumulation of LPO products in the medium--by 88%, 67%, 38%, 52%, and 47%, respectively, after incubation of LDL with monocytes, and by 65%, 47%, 41%, 65%, and 100% after incubation of LDL with neutrophils. These results indicate that activation of monocytes and neutrophils by oxidized LP intensifies LPO which proceeds via a free-radical mechanism that is superoxide-dependent and is catalyzed by transition metals.

Adult↗
PubMed1991

[Structural and functional aspects of erythrocyte membrane in children, delivered with asphyxia].

Serum and red blood cell membrane lipid peroxidation (LPO), antioxidative activity (AOA) of the ceruloplasmin/transferrin (CP/TF) system, and biophysical parameters of the structure of a red blood cell membrane lipid bilayer were examined in fetuses experienced acute hypoxia at birth and in babies born to healthy mothers with uncomplicated pregnancy. The intensity of LPO product accumulation in mild asphyxia was ascertained to be proportional to the duration of hypoxic exposure of a fetus. In severe asphyxia accompanied by lower formation of primary LPO products, the levels of secondary LPO products showed a rise. A slight increase of AOA in the CP/TF system was unable to adequately compensate a high intensity of LPO processes, which provides strong evidence for altered structural parameters in the lipid bilayer. It was concluded that it was essential to correct hypoxic states in children with antioxidants immediately after birth.

Antioxidants↗
PubMed1990

[Measurement of superoxide radicals produced by human activated neutrophils by accumulation of stable nitroxide radicals detected by MR spectroscopy].

An important index of neutrophil function is the production of superoxide radicals (O2-) upon activation. Thus a development of a new adequate assay of O2- generation measurement is of great interest for phagocyte researchers. The present article considers the quantitative determination of O2- generation based on the interaction of O2- with 1-oxy-2,2,6,6-tetramethyl-4-oxypiperidine producing 4-oxo-2,2,6,6-piperidine-1-oxyl, detected by ESR. The kinetic curve of nitroxyl radical (NR) formation has a linear character. The NR formation rate after a short induction period (appr. 2 min.) approaches 3.3 X 10(-3) M/s, where cell concentration was 4 X 10(5) per ml. Hydroxylamine (3.8 mM) auto-oxidation rate is negligible as compared with activated neutrophils and is equal to 2 X 10(-9) M/s. Sensitivity NR to the presence of superoxide dismutase (SOD) came as evidence that NR formation is due O2- radicals. SOD (10(-7) M) inhibits NR formation by 90%. Hydroxylamine oxidation by O2- is an irreversible reaction--20-min incubation of activated neutrophils with NR do not influence NR concentration. The NR generation rate dependence upon the neutrophil concentration is linear in the cell concentration range from 4 X 10(5 up to 6 X 10(6) per ml. In this range a quantitative measurement of O2- production is suitable. The sensitivity of hydroxylamine assay is close to the sensitivity of chemiluminescent method, but specificity is higher, as SOD inhibits chemiluminescence only by 50%.

Free Radicals↗
PubMed1990

[Caused of intensified lipid peroxidation in the blood of patients with viral hepatitis B].

The tissue oxygen concentration, the serum antioxidant system state and the serum malondialdehyde (MDA) concentration were studied in patients with hepatitis B. The good correlations were studied in patients with hepatitis B. The good correlations between MDA concentration in patients serum and the oxygen concentration in tissues (R-0.79), and the cytoplasmic enzymes activity (R-0.75 for lactate dehydrogenase; R-0.75 for alanine transferase) were found. On the other hand, it was shown an antioxidant activity decrease of ceruloplasmin-transferrin system in patients serum. It is proposed, that the tissue hypoxia and the decrease of the serum antioxidant activity are the general factors leading to the MDA accumulation in the serum of patients with hepatitis B.

Adolescent↗
PubMed1990

[Ceruloplasmin-transferrin antioxidant system in in experimental and clinical atherosclerosis].

The antioxidative system (AOS) ceruloplasmin-transferrin (Cp-Tr) was studied by means of electron paramagnetic resonance in 14 rabbits with experimental atherosclerosis and in 33 patients with ischemic heart disease (IHD). A correlation was found between the AOS Cp-Tr activity and the pathological process severity: mild disease was associated with high AOS activity, while in severe disease course, this activity was threefold lower. This regularity was detectable both in experimental animals and in human IHD patients. It was found that hemosorption (HS) exerted a positive effect only in the presence of low AOS Cp-Tr activity which increased after HS in these cases. In high AOS activity HS caused deterioration of the patients' condition and accumulation of lipid peroxidation products in the blood plasma; this was attended with lowering of the AOS Cp-Tr activity.

Adult↗