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Biomedical subjects

E B Lishnevskaia

Publications and source records attributed to E B Lishnevskaia.

At least 19 recordsLinked to original sources

[Inhibition of oleandomycin biosynthesis by glucose].

The results of the study on the effect of glucose and various carbohydrates on biosynthesis of oleandomycin by Streptomyces antibioticus are presented. It was found that glucose added at the beginning or by the 48th hour of the fermentation process on the complex medium inhibited oleandomycin biosynthesis. To investigate the mechanism of the glucose effect, a fermentation medium was developed. It provided variation of the carbohydrate composition, determination of the protein content in the culture and evaluation of the mycelium productivity. With the use of this medium it was shown that monosaccharides such as galactose, fructose and glucose significantly activated the mycelium growth as compared to lactose and sucrose. At the same time glucose completely inhibited oleandomycin biosynthesis when added either as an only carbohydrate component or in combination with galactose or fructose, while the presence of the other two monosaccharides did not prevent antibiotic production, though the mycelium productivity was lowered as compared to that with the use of the disaccharide. Therefore, the inhibitory effect of glucose on biosynthesis of oleandomycin was not connected with activation of the culture growth by it. Acidification of the medium on cultivation of the streptomycete in the presence of glucose only partially explained its inhibitory effect, since inhibition was maintained on the medium with addition of CaCO3 which stabilizes pH. Addition of 2-deoxy-D-glucose, a nonmetabolized glucose analog, to the fermentation medium retarded antibiotic production. It is possible that the inhibitory effect of glucose on biosynthesis of oleandomycin is not associated with its metabolism.

Culture Media↗

[Heterogeniety of the amino acid pool for protein synthesis in Ehrlich ascites carcinoma cells].

Using a new methodological approach based on a step-wise labelling with [14C] and [3H] amino acids, it was demonstrated that the Ehrlich ascite carcinoma cells are capable of utilizing both intracellular and extracellular amino acid pools for protein synthesis. The inhibition of amino acid transport into the cells is accompanied by a more intensive utilization of the exogenous pool. The described procedure permits to calculate the specific radioactivity of the tRNA-bound amino acid and the absolute rate of protein synthesis.

Amino Acids↗

[Effect of levorin on RNA synthesis in Ehrlich ascites carcinoma cells].

The polyene antibiotic levorin had no effect on the incorporation of 14C-uracil into the pool of intracellular free nucleotides in Ehrlich ascites tumour cells. RNA synthesis was inhibited by the antibiotic only at the late stages of incubation, evidently, due to earlier disturbances of the protein synthesis and in cell energetics.

Animals↗

[Effect of levorin on the intracellular pool of free amino acids in Ehrlich ascites carcinoma cells].

Levorene, a polyenic antibiotic, lowered the concentration of amino acids in the cells of Ehrlich carcinoma. The decrease in the intracellular level of the amino acids was due not only to inhibition of their entrance to the cells but also to their increased leaching from the cells. The effect of levorene on the intracellular level of the neutral amino acids was higher than that on the main amino acids which was associated with different sensitivity of the amino acid transport systems to the antibiotic.

Amino Acids↗

[Action of levorin on the incorporation of labelled amino acids into the proteins of Ehrlich ascitic cancer cells].

A polyenic antibiotic levorin had a significant damaging effect on the amino acid transport in the cells of Ehrlich's ascites carcinoma by inhibiting the incorporation and increasing the release of 14C-glycine and 14C-arginine. Inhibiton of incorporation of the radioactive amino acids into protein was observed on both simultaneous addition of the antibiotic and the label into the medium and addition of previously labeled cells into radioinactive medium with the antibiotic. Since in the latter case levorin had probably no effect on the specific radioactivity of the precursor, it was suggested that the decrease in the label incorporation into protein was an evidence of the real antibiotic inhibition of the rate of the synthesis of the polypeptide chain.

Amino Acids↗

[Effect of levorin on the activity of facilitated diffusion systems in murine Ehrlich cancer cells].

Five-minute incubation of the cells of Ehrlich's mouse carcinoma with levorin in a concentration of 0.25 microgram/ml resulted in a release of 30% of K+ and 40-50% suppression of active transport of neutral amino acids. No changes in incorporation of nitrous compounds, nucleosides and cyclophosphamide, an antitumor drug transported by the systems of facilitated diffusion were observed under the same conditions.

Amino Acids↗

[Effect of levorin on incorporation of individual amino acids into proteins of membranes, ribosomes and cell sap of Candida albicans].

The effect of levorin on incorporation of labelled amino acids into the protoplasts and proteins of C. albicans depended on the ionic composition of the medium and on the amino acid tested. In a potassium-enriched medium the predominant effect of levorin on [14C] alanine transport into the protoplasts was decreased, while in case of [14C] leucine transport it was completely eliminated. The incorporation of [14C] alanine into the proteins of ribosomes and cell juice was inhibited by the antibiotic in a greater degree as compared to the membrane proteins, the difference in the rate being more pronounced in a sodium-enriched medium. The incorporation of [14C] leucine was inhibited in all protein fractions in the same degree, which was observed only in a sodium-enriched medium.

Alanine↗

[Effect of ionic composition of incubation medium on inhibition by levorin of amino acid transfer in Candida albicans].

It was demonstrated that K+ and Na+ concentrations in C. albicans cells cultivated on an aerated enriched complex medium do not practically depend on their concentration ratios in the medium. The effect of levorin on the ionic composition of the cells, on the contrary, strongly depends on the composition of the medium. In a Na-containing medium with levorin the bulk of intracellular potassium is substituted by sodium, while in a "potassium" medium no redistribution of the monovalent cations in the cells occurs. The transport of neutral amino acids with a short carbohydrate radical (e. g. glycine, alanine) is largely inhibited by levorin irrespective of the intra- and extracellular concentrations of the movement cations. The inhibition of transport of amino acids with a long carbohydrate radical (e. g. leucine, phenylalanine) by levorin is possibly mediated by its effect on the intracellular concentration of monovalent cations, since in "potassium" medium it is either insignificant or altogether absent. The transfer of neutral amino acids differing in the length of the carbohydrate radical of C. albicans by various systems is discussed.

Amino Acids↗

[Action of levorin on glucose transport in the rat small intestine].

The technique of accumulating preparation of the mucosa and "turned out sac" was used to show that levorin, a polyenic antibiotic in a concentration of 10(-6) M, lowered the transport rate and accumulation of glucose by the epithelial cells of the rat thin intestine under conditions of oxygenation. Suppression of the glucose transport in the first stages resulted in partial inhibition of the transmembrane transfer. It is suggested that levorin suppression of the glucose transport through the erythrocyte apical membrane in the thin intestine is associated with a decrease in the electrochemical gradient of Na+.

Animals↗

[Action of levorin on amino acid transport in the rat small intestine].

Levorin, a polyenic antibiotic, in concentration of 2.10(-6) M markedly inhibited the active transport of amino acids in the cells of rat thin intestine, thus decreasing the oxygen dependent transfer of 14C-glycine and 14C-leucine and antigradient accumulation of glycine in the enterocytes. The effect increases with an increase in the period of the intestine mucosa contact with the antibiotic. Introduction of levorin from th serous side had no effect on the glycine transport. Inhibition of the transmembrane transport of glycine by levorin is due to its effect on transfer and accumulation of amino acids in the cells.

Amino Acids↗

[Action of levorin on amino acid transport in Candida albicans].

It was shown that suppression by levorin of the leucine transport into the cells of C. albicans was due to replacement of intracellular K+ by Na+ induced by the antibiotic. The alanine transport was suppressed by levorin irrespective of the ratio of the monovalent cations concentration in the medium and inside the cell. The levorin effect on the protone escape from the cells was negligible and probably played no significant role in the mechanism of the amino acid transport suppression by the antibiotic.

Alanine↗

[Doses levorin display an antiandrogenic action?].

The antiandrogenic effect of levorin on immature castrated rats treated with exogenic testosterone was studied. In a dose of 200 mg/kg levorin lowered the cholesterin blood levels in the rats, inhibited the testosterone-induced increase in RNA concentration in the ventral and dorsal prostate and the seminal vesicles and to a less extent suppressed the growth of the accessory sexual glands. However, the antiandrogenic effect was observed with the use of levorin in the dose producing a pronounced toxic action evident from death of a part of the animals and a marked decrease in the animal body weight. This fact casts doubt on specificity of the levorin effect. Apparently, in high doses levorin impairs metabolism as a whole which cannot but affect the response of the sexual glands to administration of testosterone.

Androgen Antagonists↗

[Dependence of inhibition by levorin of amino acid incorporation into protoplasts and subcellular proteins of Candida albicans on the change of endocellular potassium concentration].

Levorin is found to decrease more efficiently potassium concentration in C. albicans protoplasts under their incubation in the presence of sodium than in the medium containing the equivalent amount of potassium. Minimal inhibitory concentration of levorin for resistant C. albicans cells incubated on potassium-depeleted medium was in 4 times lower than for cells incubated in potassium-enriched medium. The decrease of membrane permeability for 14C-amino acids and their incorporation into membrane, ribosomal and soluble proteins under the effect of levorin was more pronounced when protoplasts were cultivated in sodium-containing medium than in potassium-containing one. In both media the inhibition of 14C-amino acid incorporation by levorin into ribosomal and cytosol proteins was more efficient than into membrane proteins, but these differences were less pronounced in case of potassium-containing medium.

Antifungal Agents↗

[Effect of amigluracil and levorin on membrane permeability and protein synthesis in Candida albicans protoplasts].

It was shown that amigluracyl, a water soluble derivative of methacyl which decreased the nephrotoxic effect of polyens activated the membrane permeability in Candida albicans for a mixture of 14C-amino acids but had no significant effect on protein synthesis in this microorganism. The level of inhibition of the membrane permeability in C. albicans for the amino acids and protein synthesis in the fungus by levorin did not practically depend on the presence of amigluracyl in the incubation medium. The minimum levorin concentration inhibiting the growth of Candida albicans in the presence or absence of levorin was 0.039 gamma/ml. Therefore, amigluracyl may be used in combination with polyenic antibiotics for the treatment of mycoses.

Amino Acids↗

[Effect of polyene antibiotics on protein synthesis by free and membrane-bound ribosomes of Candida albicans].

Polyene antibiotics (levorin, nistatin, amphotericin B) inhibit protein synthesis at concentrations decreasing 14C-amino acid incorporation into Candida albicans protoplasts by 30--60%, the depression of membrane permeability beginning earlier than protein synthesis inhibition. Fractionation of protoplast lysates revealed that protein synthesis by free ribosomes was inhibited by antibiotics stronger than in case of membrane-bound ribosomes. It is supposed that different response of two ribosome classes for polyenes-induced damages is due to different sensitivity of free and membrane-bound ribosomes to the decrease of intracellular K+ concentration.

Amphotericin B↗