Koltsov Institute of Developmental Biology

Moscow, Russia

Koltsov Institute of Developmental Biology

Moscow, Russia
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Aflyatumova G.N.,Childrens Republican Clinical Hospital | Sadykova D.I.,Kazan State Medical Academy | Nigmatullina R.R.,Kazan State Medical University | Chibireva M.D.,Koltsov Institute of Developmental Biology
Arterial Hypertension (Russian Federation) | Year: 2017

Objective. The aim of the study was to evaluate endothelial dysfunction based on the blood concentration of endothelin 1 (ET-1), nitric oxide (NO), serotonin (5-HT) in essential hypertension (EHTN) in adolescents and in experimental animal models. Design and methods. The work was carried out in two stages. The clinical part was preceded by the investigation of experimental models of arterial hypertension (HTN). Twenty five immature male SHR rats aged 6-7 weeks and 10 immature male Wistar-Kyoto rats aged 6-7 weeks (control group) were examined. The clinical part of the study included 70 untreated male adolescents (mean age 15,63 ± 0,26 years), among them 24 people had a labile form of EHTN (LHTN), 30 had stable form of EHTN (SHTN), the control group included 16 subjects. All participants underwent 24-hour blood pressure monitoring. The plasma concentration of EN-1 (ET-1) was determined by enzyme immunoassay, total concentration of stable metabolites of NO, 5-HT in serum and platelets was measured. Results. The serum levels of ET-1 and 5-HT were higher in HTN groups than in the control group, and in adolescents with SHTN levels of both indices were higher compared to those with LHTN (p < 0,0001). Serotonin level in platelets in HTN groups was lower than in the control group (p < 0,0001). Compared to the control group, NO levels were higher in adolescents with LHTN, but lower in patients with SHTN (p < 0,0001). The changes in the level of ET-1, 5-HT and NO in plasma, serum and blood platelets in the experimental animal model were similar to those found in patients with labile and stable HTN. Conclusions. NO, ET-1 and 5-HT are early sensitive markers of endothelial dysfunction in EHTN in adolescent males, as well as in the experimental SHR rat model.


Bondarenko N.S.,Koltsov Institute of Developmental Biology | Shneiderman A.N.,Institute of Carcinogenesis | Guseva A.A.,Moscow State University | Umarova B.A.,Moscow State University
Acta Naturae | Year: 2017

This study was aimed at investigating the effect of prolyl-glycyl-proline (PGP) tripeptide on vascular permeability in rats with an inflammation. It was found that the peptide reduces the rat paw edema induced by a subcutaneous administration of histamine to the same extent as the conventional anti-inflammatory agent diclofenac. However, an assessment of the relative expression level of the cox-2 gene at the inflammation focus using real-time PCR showed that, in contrast to diclofenac, PGP does not affect the cox-2 gene expression. This is indicative of the fact that they have different mechanisms of action. We used the model of acute peritonitis induced by an intraperitoneal injection of thioglycolate to demonstrate that the inflammatory response of an organism is accompanied by increased vascular permeability in the tissues of the stomach and small intestine. Pre-administration (30 minutes before the induction of the inflammation) of PGP prevented this increase, whereby the level of vascular permeability, exudate volume in the peritoneal cavity, and the amount of the Evans Blue dye in this exudate remained at the control level. Therefore, these results suggest that the anti-inflammatory action of PGP is based on its ability to prevent an increase in vascular permeability. © 2017 Park-media, Ltd.


Pavlyuchenkova S.M.,Moscow State University | Zakhidov S.T.,Moscow State University | Makarov A.A.,National Research University Higher School of Economics | Marshak T.L.,Koltsov Institute of Developmental Biology
Biology Bulletin | Year: 2012

It has been shown that a single intratesticular injection of the chemical mutagen dipin (experiment) or saline (control) into mice resulted in significant but reversible morphohistological damage of the spermatogenic epithelium. However, unlike the controls, in mutagenized testes these damages were more pronounced. Thus, the process of restoring a normal pattern of spermatogenesis was slower. In addition, on day 35 of fixation, mature gametes were almost completely absent in the cauda epididymis and a large number of sperm cells with abnormal head shape (58.5 versus 1.7% in the controls) appeared in the testes. Using spermatogonial and meiotic micronucleus assay, we found that dipin did not induce a rise in the number of gross chromosomal mutations in the spermatogonial stem cells (SSCs): on days 35, 56, and 100 postinjection, the incidence of aberrant spermatogonia and round spermatids was not significantly different from the saline control. The degree of gametic chromatin decondensation was evaluated after treatment of the cauda epididymal sperm with sodium dodecyl sulfate (SDS) and dithiothreitol (DTT). Judging by the results of the in vitro sperm chromatin decondensation on days 7, 14, 35, 56, and 100 after the injection of dipin or saline, the number of decondensed nuclei decreased sharply in the studied samples as compared with the sperm from intact animals where sperm cells with fully decondensed chromatin prevailed. © 2012 Pleiades Publishing, Ltd.


Zakharova L.A.,Koltsov Institute of Developmental Biology
Russian Journal of Developmental Biology | Year: 2010

Cross-regulatory effects of immune and neuroendocrine systems on their appearance and functioning occur during a whole life period. At different stages of ontogenesis, the functions of these systems are diverse. In perinatal ontogenesis hormones, neuropeptides and neurotransmitters control the processes of growth and differentiation of various embryo tissues, particularly lymphoid. In the postnatal period, their functions are mostly in homeostasis maintaining of the immune system in response to changes of the environment. Conversely, transmitters of the immune system, such as cytokines, whose synthesis is increased in inflammation, and thymic peptides, program the development of the neuroendocrine system of the embryo. The perinatal period is crucial for final appearance of these systems. Changes in one of the interacting systems, caused by negative environmental factors at this stage, usually provoke changes in other developing systems for a long period. Plasticity of physiological systems in perinatal development allows the organism to adapt to changed conditions. However, these changes can limit physiological functions in interacting systems and induce the appearance of various pathologies in postnatal life. © 2010 Pleiades Publishing, Ltd.


Voronezhskaya E.E.,Koltsov Institute of Developmental Biology | Ivashkin E.G.,Koltsov Institute of Developmental Biology
Russian Journal of Developmental Biology | Year: 2010

It has been demonstrated by us and other authors that first nervous cells in developing larvae from various trochozoan groups differentiate at the periphery. These pioneer neurons are distinguished by the set of characters. They are located outside the forming central ganglia; outgrowing fibers of central neurons use their processes as a "scaffolding" transmitter expression in these neurons is transient. On the one hand, pioneer neurons mark the "frame" of the adult nervous system and thus play a limiting role. On the other hand, pioneering navigation provides possible mechanisms for evolutional plasticity of the nervous system in adults. In addition, pioneer neurons can underlie functional adaptation of trochophore animals, which minimizes fitness decrease during the transition from the larval to the adult form during metamorphosis. © 2010 Pleiades Publishing, Ltd.


A structural analysis of two lactate dehydrogenase M4 protein forms has been performed. These structures are the protein products of two lactate dehydrogenase gene (LDH-A) copies in the weatherfish Misgurnus fossilis genome after thermal adaptation (acclimation) to 5°C and 18°C. The localization of three earlier identified amino acid substitutions (Gly214Val, Leu304Ile, Asp312Glu) has been determined, and the molecular dynamics simulation and computer modeling of two forms of the enzyme from skeletal muscles LDH-M4 have been carried out. After molecular dynamics trajectory calculations carried out at 5, 18, and 25°C, the intersubunit distances for all structures used in calculations have been determined. It has been found that the Gly214Val substitution localized in the intersubunit region leads to a new intersubunit interaction, which plays a role in the stabilization of tetrameric enzyme structure after the adaptation to 18°C. © 2011 Pleiades Publishing, Ltd.


Gnedeva K.,Sanford Burnham Institute for Medical Research | Gnedeva K.,Koltsov Institute of Developmental Biology | Vorotelyak E.,Koltsov Institute of Developmental Biology | Cimadamore F.,Sanford Burnham Institute for Medical Research | And 4 more authors.
PLoS ONE | Year: 2015

Dermal Papillae (DP) is a unique population of mesenchymal cells that was shown to regulate hair follicle formation and growth cycle. During development most DP cells are derived from mesoderm, however, functionally equivalent DP cells of cephalic hairs originate from Neural Crest (NC). Here we directed human embryonic stem cells (hESCs) to generate first NC cells and then hair-inducing DP-like cells in culture. We showed that hESC-derived DPlike cells (hESC-DPs) express markers typically found in adult human DP cells (e.g. p-75, nestin, versican, SMA, alkaline phosphatase) and are able to induce hair follicle formation when transplanted under the skin of immunodeficient NUDE mice. Engineered to express GFP, hESC-derived DP-like cells incorporate into DP of newly formed hair follicles and express appropriate markers. We demonstrated that BMP signaling is critical for hESC-DP derivation since BMP inhibitor dorsomorphin completely eliminated hair-inducing activity from hESC-DP cultures. DP cells were proposed as the cell-based treatment for hair loss diseases. Unfortunately human DP cells are not suitable for this purpose because they cannot be obtained in necessary amounts and rapidly loose their ability to induce hair follicle formation when cultured. In this context derivation of functional hESC-DP cells capable of inducing a robust hair growth for the first time shown here can become an important finding for the biomedical science. Copyright © 2015 PLOS.


Goncharov B.F.,Koltsov Institute of Developmental Biology | Skoblina M.N.,Koltsov Institute of Developmental Biology
Russian Journal of Developmental Biology | Year: 2014

Incubation of sturgeon full-grown ovarian follicles in amphibian Ringer solution with increased sodium bicarbonate concentration results in "spontaneous" oocyte maturation. Addition of sodium bicarbonate to diluted Leibovitz medium also induces maturation of follicle-enclosed oocytes. Effective threshold concentration of sodium bicarbonate depends on the composition of culture medium and, especially, on the physiological state of follicle-enclosed oocytes. As evidenced by experiments with actinomycin D, oocyte maturation induced by bicarbonate ions does not depend on RNA synthesis. An attempt was made to elucidate the involvement of steroidogenesis in bicarbonate ions-induced oocyte maturation. Surprisingly, the inhibitors used, such as aminoglutethimide, diltiazem, and estradiol-17β, not only did not inhibit but also enhanced oocyte maturation. Manual removal of follicle envelopes demonstrated that denuded oocytes retained the ability to mature in a culture medium with increased sodium bicarbonate concentration. However, the range of effective bicarbonate ion concentrations for denuded oocytes is more restricted than for the follicle-enclosed oocytes. A hypothesis of competition of different processes occurring in the ovarian follicle for energy resources is proposed to explain the revealed paradoxical effect of substances affecting steroidogenesis. © 2014 Pleiades Publishing, Inc.


Shabarina A.N.,Koltsov Institute of Developmental Biology
Genetika | Year: 2013

The results of investigating the functions of different barrier elements, including insulators and MARs/SARs and the models of their effect, are described. The functions of neDNA (DNA from the nuclear envelopes) as a barrier element that protects the transgene from position-effect variegation and its interaction with insulators are discussed. The possible mechanisms of the functioning of structural and functional units of eukaryotic chromosomes of different species are suggested.

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