Plasmolipin and Its Role in Cell Processes

Molecular Biology - The mechanisms involved in the origin and development of malignant and neurodegenerative diseases are an important area of modern biomedicine. A crucial task is to identify new...     

The effect of 3,5-dicarbomethoxyphenylbiguanide on the activity of antioxidant enzymes

The effect of 3,5-dicarbomethoxyphenylbiguanide, which was selected with the Prediction of Activity Spectra of Substances (PASS) computer program, on the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione transferase in the heart and the blood serum of rats with experimental rheumatoid arthritis was investigated. The studied parameters changed towards control values when the tested compound was injected in animals with the pathology. These results can be explained by the cardioprotective and antioxidant activity of the compound. The data obtained during the study may be used for the development of new preventive and therapeutic agents for the treatment of the rheumatoid arthritis.     

Relationship between preferential interaction of a protein in an aqueous mixed solvent and its solubility

The present paper is devoted to the derivation of a relation between the preferential solvation of a protein in a binary aqueous solution and its solubility. The preferential binding parameter, which is a measure of the preferential solvation (or preferential hydration) is expressed in terms of the derivative of the protein activity coefficient with respect to the water mole fraction, the partial molar volume of protein at infinite dilution and some characteristics of the protein-free mixed solvent. This expression is used as the starting point in the derivation of a relationship between the preferential binding parameter and the solubility of a protein in a binary aqueous solution. The obtained expression is used in two different ways: (1) to produce a simple criterion for the salting-in or salting-out by various cosolvents on the protein solubility in water, (2) to derive equations which predict the solubility of a protein in a binary aqueous solution in terms of the preferential binding parameter. The solubilities of lysozyme in aqueous sodium chloride solutions (pH=4.5 and 7.0), in aqueous sodium acetate (pH=8.3) and in aqueous magnesium chloride (pH=4.1) solutions are predicted in terms of the preferential binding parameter without any adjustable parameter. The results are compared with experiment, and for aqueous sodium chloride mixtures the agreement is excellent, for aqueous sodium acetate and magnesium chloride mixtures the agreement is only satisfactory.     

Effects of Salicylic Acid and Its Salts on Electrical Activity of Neurons of <Emphasis Type="Italic">Helix albescens</Emphasis>

We studied changes in the parameters of electrical activity of identified neurons of the parietal ganglion, PPa1 and PPa2, and of non-identified cells of the visceral ganglion (VG) of the snail Helix albescens; these changes were caused by application of salicylic acid and its salts (cobalt and zinc salicylates, CS and ZS, respectively). The above substances began to modify significantly the functional state of the neurons under study when applied in concentrations of 10⁻⁴ to 10⁻³ M. Salicylic acid suppressed the activity of all studied neurons. Application of salicylic acid in the concentration of 10⁻³ M led to a decrease in the impulsation frequency of VG neurons by factors of 1.2 to 1.5 and to an increase in the duration of AP (on average, by 2.8 ± ± 0.6 msec). In PPa1 and PPa2 cells, we observed increases in both the AP duration (by 2.4 ± 0.8 and 3.6 ± ± 1.3 msec, respectively) and that of postactivation hyperpolarization (by 29.8 ± 11 0 and 39.6 ± 9.4 msec). In the concentration of 10⁻² M, salicylic acid completely but relatively reversibly suppressed the impulse activity of all the neurons under study, causing deep hyperpolarization of their membranes. Salts of this acid, CS and ZS, demonstrated significant modulatory effects on the activity of the studied neurons; these substances initiated or enhanced the grouping of APs in bursts and also increased the AP duration. Application of 10⁻³ M CS resulted in an increase in the AP duration by, on average, 2.75 ± 0.4 msec (only in the PPa2 neuron), whereas 10⁻³ M ZS exerted analogous effects on both above neurons (in PPa1, by 2.7 ± 0.4, while in PPa2, by 3.1 ± 0.6 msec). In the case where the tested salicylates were applied in the concentration of 10⁻² M, the AP duration increased in all the cells under study (on average, by 11.8 ± 2.46 msec in VG neurons, and by 7.0 ± ± 0.4 and 7.8 ± 1.2 msec in PPa1 and PPa2 cells, respectively). With application of CS, analogous values determined by application of ZS were 14.6 ± 4.6, 6.8 ± 0.54, and 9.0 ± 0.89 msec. We assume that the modulatory effects of salicylates are mediated by their influence on the intracellular system of cyclic nucleotides. Neirofiziologiya/Neurophysiology, Vol. 37, No. 2, pp. 142–150, March–April, 2005.     

Preferential hydration and solubility of proteins in aqueous solutions of polyethylene glycol

This paper is focused on the local composition around a protein molecule in aqueous mixtures containing polyethylene glycol (PEG) and the solubility of proteins in water + PEG mixed solvents. Experimental data from literature regarding the preferential binding parameter were used to calculate the excesses (or deficits) of water and PEG in the vicinity of β-lactoglobulin, bovine serum albumin, lysozyme, chymotrypsinogen and ribonuclease A. It was concluded that the protein molecule is preferentially hydrated in all cases (for all proteins and PEGs investigated). The excesses of water and deficits of PEG in the vicinity of a protein molecule could be explained by a steric exclusion mechanism, i.e. the large difference in the sizes of water and PEG molecules.

The solubility of different proteins in water + PEG mixed solvent was expressed in terms of the preferential binding parameter. The slope of the logarithm of protein (lysozyme, β-lactoglobulin and bovine serum albumin) solubility versus the PEG concentration could be predicted on the basis of experimental data regarding the preferential binding parameter. For all the cases considered (various proteins, various PEGs molecular weights and various pHs), our theory predicted that PEG acts as a salting-out agent, conclusion in full agreement with experimental observations. The predicted slopes were compared with experimental values and while in some cases good agreement was found, in other cases the agreement was less satisfactory. Because the established equation is a rigorous thermodynamic one, the disagreement might occur because the experimental results used for the solubility and/or the preferential binding parameter do not correspond to thermodynamic equilibrium.     

The effect of melaxen and valdoxan on the activity of the glutathione antioxidant system in rats with experimental hyperthyroidism

The activity of the glutathione system and conjugated diene content (CD) have been investigated in the liver and blood serum of rats with experimental hyperthyroidism treated with melaxen and valdoxan. The study of glutathione reductase (GR), glutathione peroxidase (GP) and glutathione transferase (GST) activities increased under this pathology has shown that administration of these compounds decreased these activities towards control levels. Melaxen and valdoxan administration increased reduced glutathione (GSH) content as compared with untreated hyperthyroid rats. This increase may be associated with its decreased utilization for detoxification of toxic products of free radical oxidation (FRO). Administration of the melatonin correcting drugs also tended to normalize the CD level increased in the liver and blood serum of hyperthyroid rats. Results of this study indicate that melaxen and valdoxan exhibit positive effect on free radical homeostasis. This appears to be accompanied by a decrease in the load of the glutathione antioxidant system in comparison with the examined pathology.     

Isolation and purification of glutathione peroxidase

Electrophoretically homogeneous glutathione peroxidase (EC 1.11.1.9) preparation from rat liver with a specific activity of 1.46 U/mg of protein and a yield of 7.2% was obtained using the purification procedure developed. The K _M values for reduced glutathione and hydrogen peroxide were 0.033 and 0.208 mM, respectively. The enzymatic reaction had the following characteristics: the temperature optimum, 32°C; the pH optimum, 7.4; and the activation energy, 29.1 kJ/mol. The molecular weight of the enzyme was 88 kDa.     

Effects of Melatonin‐Aided Therapy on the Glutathione Antioxidant System Activity and Liver Protection

Acute hepatitis results from oxidative stress triggered by hepatotoxic drugs causing liver injury and the activation of caspases cascade. The glutathione antioxidant system protects against reactive oxygen species and mitigates development of these processes. The effectiveness of silymarin, a polyphenolic flavonoid, essenthiale, composed of phosphatidyl choline, and melaxen, a melatonin‐correcting drug, as hepatoprotectors has been investigated. The variation of 6‐sulfatoxymelatonin (aMT6s), resulting from the biotransformation of melatonin, and GSH has been measured. The activities of caspase‐1 and caspase‐3, glutathione antioxidant system, and NADPH‐generating enzymes were determined. The aMT6s decreases in patients with drug hepatitis and recovers with administration of mexalen. GSH increased in the presence of the studied hepatoprotectors. Pathologically activated caspase‐1 and caspase‐3 decreased their activities in the presence of hepatoprotectors with melaxen showing the highest effect. The positive effect of melatonin appears to be related to the suppression of decompensation of the glutathione antioxidant system functions, recovery of liver redox status, and the attenuation of inhibition of the NADPH supply.