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Biomedical subjects

R P Evstigneeva

Publications and source records attributed to R P Evstigneeva.

At least 19 recordsLinked to original sources

Effects of reduced and oxidized glutathione on sphingomyelinase activity and contents of sphingomyelin and lipid peroxidation products in murine liver.

Like the phosphatidyl inositol cycle, the sphingomyelin cycle produces a series of the secondary messengers transmitting extracellular signals from the cytoplasmic membrane into the nucleus. Sphingomyelin, ceramide, sphingosine, sphingomyelinase, and ceramidase are the main components of the sphingomyelin cycle. In spite of numerous data on the functional properties of sphingomyelin cycle products, the activation mechanism for the key enzyme of the sphingomyelin cycle, sphingomyelinase (SMase), is not well understood. We have discovered effects of both reduced (GSH) and oxidized (GSSG) glutathione on the activity of neutral SMase in animals. GSH administration (18 mg per mouse) inhibits this enzymatic activity in liver for 2 h and increases the sphingomyelin level exactly as occurs in cell culture. The levels of diene conjugates and ketodienes decrease simultaneously during the experiment, thus indicating the ability of GSH to suppress oxidative processes in the cell. GSSG administration (18 mg per mouse) has no effect on the SMase activity during the first 15 min, but increases it twofold after 1 h. A short-term decrease in this activity after 30 min may depend on the conversion of excess GSSG into its reduced form by glutathione reductase. Unlike GSH, GSSG has no effect on the level of ketodienes after 1 h, but it induces the accumulation of diene conjugates. A strong correlation exists between the changes in SMase activity and in the level of oxidation products caused by either GSH or GSSG. These data indicate a relationship between SMase activity and the level of peroxidation products and possibly a relation between two signaling systems: the sphingomyelin cycle and the oxidative system.

Animals↗

Photophysical properties of carborane-containing derivatives of 5,10,15,20-tetra(p-aminophenyl)porphyrin.

Absorption, fluorescence emission, fluorescence excitation spectra and fluorescence decay kinetics of carborane derivatives of 5,10,15,20-tetra(p-aminophenyl)porphyrin have been investigated. Carborane derivatives are prepared by acylation of the amino groups of 5,10,15,20-tetra(p-aminophenyl)porphyrin by 9-carboranyl acetyl chloride. From the analysis of the absorption and fluorescence spectra, it is concluded that covalent linking of carborane molecules to the tetraphenylporphyrin molecule significantly changes the self-conjugated pi-system of the porphyrin macrocycle: positions of maxima of absorption and fluorescence spectra shift to the red region by 3-8 nm; the halfwidths of these bands are broadened by 2.5-5.0 nm; the relative intensity of the bands I-IV also changes. The fluorescence decay kinetics of the carborane derivatives are biexponential. According to the experimental data and model simulation, it is concluded that the intramolecular electron transfer proceeds from the porphyrin excited part of the molecule to carboranyls with a rate constant of 415 ps(-1) and efficiency of 0.16-0.8. Recombination of separated charges occurs within 1.4 ns.

Boranes↗

[Methods of searching for antigenic determinants for proteins with known primary structure].

Theoretical and experimental methods for locating antigenic determinants of proteins with known amino acid sequences are discussed. These methods are systematized on the basis of the theoretical approaches applied, and the efficiency of various predictive methods is compared. Some examples of experimental epitope determination for a number of proteins are given.

Amino Acid Sequence↗

[Synthesis and antioxidant activity of azole derivatives of hemin].

New derivatives of proto- and deuterohemin IX containing tri- and tetrazole rings were synthesized and characterized. A pronounced antioxidant activity was found for these compounds in the Fe(II)/ascorbate-dependent system of lipid peroxidation in murine liver homogenates.

Animals↗

[Synthesis and biological properties of artificial antigens based on 280-289 fragment of beta2-gpI].

A series of artificial antigens were synthesized on the basis of the FC(Acm)KNKEKKC(Acm)S peptide from the beta 2-glycoprotein I sequence: lipophilic analogues, the peptide-BSA conjugate, and multiple antigen peptide (MAP) containing eight copies of the peptide on an oligolysyl core. The solid phase method for acylation of the peptide with fatty acids and the HPLC analysis of the acylpeptides were described. Antigenic properties of the resulting compounds were evaluated by CL-ELISA.

Acylation↗

Vitamin E as a universal antioxidant and stabilizer of biological membranes.

The known literature data concerning the mechanisms of molecular action of vitamin E in biological membrane systems are reviewed. The role of vitamin E, possessing a broad range of biological activities, as a universal stabilizer of biological membranes in normal oxygen metabolism and peroxidation, and also in disorders of normal metabolism resulting in pathological alterations, has been discussed. The participation of vitamin E in redox reactions taking place in lipid media, its interaction with singlet oxygen, free fatty acids and enzyme systems are considered. Physiological effects of vitamin E and its ability to prevent numerous pathologies are also considered. Vitamin E was concluded to be a universal participant of antioxidant defence reactions in biological membranes, since it acts at all stages of membrane oxidative damage.

Aging↗

N alpha-acetylcarnosine is a prodrug of L-carnosine in ophthalmic application as antioxidant.

The naturally occurring compound N alpha-acetylcarnosine (NAC) is proposed as the prodrug of L-carnosine (C) resistant to enzymatic hydrolysis by human serum carnosinase. Rabbit eyes were treated with 1% NAC, C or placebo and extracts of the aqueous humor from the anterior eye chamber were analyzed for imidazole content by reverse phase analytical high performance liquid chromatography (HPLC), thin-layer (TLC) and ion-exchange chromatographic techniques. The topical administration of pure C to the rabbit eye did not lead to accumulation of this compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eye. NAC showed dose-dependent hydrolysis in its passage from the cornea to the aqueous humor, releasing C after 15. 30 min of ocular administration of prodrug in a series of therapeutical modalities: instillation < or = subconjunctival injection < or = ultrasound induced phoresis. Different treatment techniques showed excellent toleration of 1% NAC by the eye. Once in the aqueous humor, C might act as an antioxidant and enter the lens tissue when present at effective concentrations (5-15 mmol/l). The advantage of the ophthalmic prodrug NAC and its bioactivated principle C as universal antioxidants relates to their ability to give efficient protection against oxidative stress both in the lipid phase of biological membranes and in an aqueous environment. NAC is proposed to treat ocular disorders which have the component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus, systemic diseases).

Animals↗

[Direct transition of S-acetamidomethyl-protected peptide 593-603 of HIV-2 gp41 into a cyclic disulfide using iodine. Study of side reactions].

Removal of Acm-protecting group from thiol functional groups of Cys residues with simultaneous disulfide bridge formation by iodine in acetic acid was studied in the course of the synthesis of a peptide fragment corresponding to 593-603 sequence of HIV-2 gp41 glycoprotein. The excess iodine influence on the cyclization process was investigated. By-products of the oxidative disulfide formation were isolated, and their structures were elucidated by means of amino acid and elemental analyses, mass spectrometry, NMR, and UV-spectroscopy.

Acetylcysteine↗

L-carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities.

Carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) are natural imidazole-containing compounds found in the non-protein fraction of mammalian tissues. Carcinine was synthesized by an original procedure and characterized. Both carnosine and carcinine (10-25 mM) are capable of inhibiting the catalysis of linoleic acid and phosphatidylcholine liposomal peroxidation (LPO) by the O2(-.)-dependent iron-ascorbate and lipid-peroxyl-radical-generating linoleic acid 13-monohydroperoxide (LOOH)-activated haemoglobin systems, as measured by thiobarbituric-acid-reactive substance. Carcinine and carnosine are good scavengers of OH. radicals, as detected by iron-dependent radical damage to the sugar deoxyribose. This suggests that carnosine and carcinine are able to scavenge free radicals or donate hydrogen ions. The iodometric, conjugated diene and t.l.c. assessments of lipid hydroperoxides (13-monohydroperoxide linoleic acid and phosphatidylcholine hydroperoxide) showed their efficient reduction and deactivation by carnosine and carcinine (10-25 mM) in the liberated and bound-to-artificial-bilayer states. This suggests that the peroxidase activity exceeded that susceptible to direct reduction with glutathione peroxidase. Imidazole, solutions of beta-alanine, or their mixtures with peptide moieties did not show antioxidant potential. Free L-histidine and especially histamine stimulated iron (II) salt-dependent LPO. Due to the combination of weak metal chelating (abolished by EDTA), OH. and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biological membranes and aqueous environments.

Antioxidants↗