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Biomedical subjects

O V Shamova

Publications and source records attributed to O V Shamova.

15 recordsLinked to original sources

alpha-Defensins from blood leukocytes of the monkey Papio hamadryas.

Three antimicrobial peptides named PHD1-3 (Papio hamadryas defensin) have been isolated from hamadryas baboon blood leukocytes using preparative electrophoresis and reverse-phase HPLC. The primary structures of these peptides have been determined by automated Edman degradation and mass-spectrometry. The results suggest that the peptides belong to the alpha-defensin family. Structural homology analysis reveals that among alpha-defensins from other animal species, PHD3 is the most closely related to RMAD5 (rhesus macaque alpha-defensin) (90% homology) from rhesus macaque leukocytes and also highly similar to human alpha-defensin HD5 (60% homology), which is produced by intestinal Paneth cells. The homology of PHD3 with human neutrophil alpha-defensin HNP1 (human natural peptide) was 30%. The primary structures of PHD1 and PHD2 are most similar to RED1 (rhesus enteral defensin), one of six enteral alpha-defensins of rhesus monkeys. PHD1-3 have been shown to be active against the Gram-positive bacteria Listeria monocytogenes and Staphylococcus aureus, the Gram-negative bacterium Escherichia coli, and the fungus Candida albicans, similarly to the human HNP1 defensin.

Amino Acid Sequence↗

[Glucocorticoid hormones in immunomodulating effect of defensins].

Defensins are a family of antimicrobial cationic peptides localized mainly in neutrophile granulocytes. The defensins are known to display corticostatic activity by means of suppression of stress- and ACTH-induced rise in corticosterone level in the blood. The present study examines influence of defensin fractions with different corticostatic activity on suppressor functions of T-lymphocytes. It was shown that corticostatic effects of defensins are revealed under an increased level of glucocorticoids in the blood after hydrocortisone application. Defensins were found to limit the inhibitory action of glucocorticoids on the suppressor functions of T-lymphocytes. After adrenalectomy this phenomenon was not observed.

Adjuvants, Immunologic↗

[Achievements and problems in studies of antibiotic peptides of an organic origin].

The paper contains the original data of the authors and literature survey in the field of studies of the structure and functions of antibiotic peptides. Physical-and-chemical as well as structural properties of a new subfamily of defensins, i.e. minidefensins (theta-defensins), are described in detail. Mechanisms of the antibiotic action of defensins and bactenecins as well as their role in regulating the body immune reactions are discussed.

Anti-Bacterial Agents↗

[Cytotoxic and mitogenic effect of antimicrobial peptides from neutrophils on cultured cells].

Cytotoxic and mitogenic activities of human and rabbit defensines (HNP and NP-2, resp.) and pig antimicrobial peptides from leukocytes (PR-39, prophenin PF-2 and protegrin PG-2) were studied. The above peptides were added to serum-free cell culture medium of the target cell lines K562, L929 and Hep22a. Cytotoxicity was estimated within 1, 3, 6, 24 and 48 h of cell incubation with the tested peptides in concentrations 1, 10, 25 or 100 micrograms/ml. All the examined peptides exhibited a distinct time- and concentration-dependent cytotoxicity. Moreover, by contrast to pig peptides, defensines could induce proliferation in cell subpopulations from cell lines L929 amd Hep22a, or L929 (defensines HNP and NP-2, resp.), keeping resistance to their cytotoxic action.

Animals↗

Interleukin-1 and defensins in thermoregulation, stress, and immunity.

Our previous studies suggested that IL-1 and defensins, which play a critical role in mechanisms of host resistance, participated in the realization of stress reaction. The present report describes functional relations between IL-1 and defensins during stress reactions and the influence of defensins administration on thermoregulation and the IL-1 level in blood. It is shown that stress-induced shifts in the humoral immune response are accompanied by diverse changes in the IL-1 alpha level in blood and LAF production by peritoneal macrophages, which are possibly associated with the intensity and strength of applied stressors. Functional interrelations between actions of defensins and IL-1 during stress reaction and in the conditions of an LPS-induced rise in body temperature was demonstrated. These results suggest that antibacterial peptides defensins may be involved in thermoregulation in case of increased body temperature probably influencing the blood level of IL-1.

Animals↗

Gallinacins: cysteine-rich antimicrobial peptides of chicken leukocytes.

We purified three homologous antimicrobial peptides ('gallinacins') from chicken leukocytes, examined their antimicrobial activity in vitro, and established their primary sequences by a combination of gas phase microsequencing and on-line LC-ESI-MS analysis of endo- and exoprotease peptide digests. The peptides contained 36-39 amino acid residues, were relatively cationic due to their numerous lysine and arginine residues, and each contained 3 intramolecular cystine disulfide bonds. Gallinacins showed primary sequence homology to the recently delineated beta-defensin family, heretofore found only in the respiratory epithelial cells and neutrophils of cattle, suggesting that beta-defensins originated at least 250 million years ago, before avian and mammalian lineages diverged. The 9 invariant residues (6 cysteines, 2 glycines and 1 proline) common to avian gallinacins and bovine beta-defensins are likely to constitute the essential primary structural motif of this ancient family of host-defense peptides.

Amino Acid Sequence↗

Primary structure of three cationic peptides from porcine neutrophils. Sequence determination by the combined usage of electrospray ionization mass spectrometry and Edman degradation.

The primary structure of three major cationic peptides from porcine neutrophils has been determined. The sequencing was made by the combined use of electrospray ionization mass spectrometry and Edman degradation. The determined sequences unambiguously show that these peptides can not be considered as defensins.

Amino Acid Sequence↗

Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins.

Porcine leukocytes contained three homologous peptides, PG-1, 2 and 3, that manifested potent microbicidal activity against Escherichia coli, Listeria monocytogenes and Candida albicans in vitro. The peptides ('protegrins') were composed of 16 (PG-2) or 18 amino acid residues, and, like tachyplesins (broad-spectrum antibiotic peptides of horseshoe crab hemocytes), they contained two intramolecular cystine disulfide bonds. Considerably smaller than defensins, protegrins nevertheless showed substantial homology to them, especially to the 'corticostatic' rabbit defensin, NP-3a. The relatively simple structure of protegrins should provide useful prototypes for constructing congeners with selectively enhanced host defense activities.

Amino Acid Sequence↗

[The action of defensins on the corticosterone level of the blood and on the immune response in stress].

The influence of defensins on the level of corticosterone in the blood and immune response in stress was studied. Defensins were shown to have corticostatic activity in vivo in the models of stress- and ACTG-induced elevation of corticosterone. Also defensins abolished the immunosuppressive action of combining stress in animals. These results suggest that defensins may be endogenic peptides with stress-protective properties.

Animals↗

[Effect of defensin on the process of healing of aseptic skin wound and on the permeability of blood vessels].

It was shown, for the first time, that polypeptide of rabbit's neutrophils, defensin (D) has the ability to accelerate the reparation process (RP). D was infused intramuscular to rats (125 micrograms/kg) 2 days before the operation, then the skin on the back was dissected through all layers (the length of the wound was constant-10 mm). The rate of the RP was estimated by the changes of the wound length on 2, 5, 7, 13-15 days after the operation. The injection of D or physiological solution was continued during 2 weeks. It was shown, that beginning from the fifth postoperative day the RP in the experimental rats developed faster, than in control rats. In the experimental group the full reparation appeared earlier, than in the control group (on 21-22 and 24-26 days correspondingly. Qualitative (with trypan blue) and semi-quantitative (with colloid coal) methods have shown, that D augmented the permeability of blood vessels. It was proposed, that the RP acceleration was induced by D augmentation of the blood vessels permeability.

Animals↗

[Interaction of heparin with defensin, a nonenzymatic cationic protein from neutrophils].

Heparin was shown to form complexes with cation non-enzymatic protein defensin from neutrophils. The complex obtained in vitro did not affect the anticoagulation and fibrinolytic properties of blood, whereas defensin decreased the content of heparin, rates of non-enzymatic fibrinolysis and total fibrinolytic activity while heparin stimulated the anticoagulation activity of blood plasma. Interaction of heparin with defensin appears to be involved in protective mechanism responsible for neutralization of both the heparin anticoagulation activity and the defensin properties related to inhibition of nonenzymatic fibrinolysis.

Animals↗

[Cationic antimicrobial peptides as molecular immunity factors: multi-functionality].

Cationic antimicrobial peptides (AMP) of mammals (defensins, cathelicidins, protegrins and many others) are regarded as important components of congenital immunity. AMP are multifunctional molecules, capable of killing microorganisms directly by acting as endogenic, natural antibiotics ("immediate immunity"); in addition, they may take part in congenital and adaptive immune reactions (immunoregulation) and function as signal molecules, involved into tissue reparation, inflammation (including sepsis), blood coagulation and other important processes in the body. The molecular mechanisms of the direct antimicrobial action of AMP are considered. In addition to antimicrobial and immunoregulating action, AMP have influence on immunoneuroendocrine interactions, taking part in the pathogenesis of stress reactions (corticostatic action), as well as play the role of regulatory peptides of adaptogenic action. The many-sided character of the action of AMP opens prospects to the creation of new medicinal remedies on their basis. Such requirements are met by the Russian preparation "Superlymph" (a complex of natural cytokines), containing protegrin-like AMP.

Adaptation, Physiological↗

[Comparative enzymologic analysis of the creatine kinases from the skeletal muscles of the cod, frog and rabbit].

Electrophoretic studies have been made of the protein composition and isozymic pattern of the creatine kinase from muscles of the cod. It was shown that this enzyme constitutes up to 40% of total water-soluble proteins of muscle tissue. Isolation and purification procedures were suggested for the creatine kinase from cod muscles which allow to obtain the enzyme with the specific activity 250-350 IU/mg. Comparative enzymic analysis of creatine kinases from muscle tissue of the cod, lake frog, and rabbit was also made. Studies were carried out on temperature dependence of the reaction, kinetic constants at temperatures 5 and 30 degrees C were determined together with other physicochemical properties of the enzymes. The revealed species specific differences are discussed in relation to the structure and function of the enzymes in lower vertebrates in vivo.

Animals↗