Institute of Cell Biophysics

Moscow oblast, Russia

Institute of Cell Biophysics

Moscow oblast, Russia
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Kenney J.W.,University of Southampton | Sorokina O.,University of Edinburgh | Genheden M.,University of Southampton | Sorokin A.,institute of Cell Biophysics | And 2 more authors.
Journal of Neuroscience | Year: 2015

The rapid regulation of cell signaling in response to calcium in neurons is essential for real-time processing of large amounts of information in the brain. A vital regulatory component, and one of the most energy-intensive biochemical processes in cells, is the elongation phase of mRNA translation, which is controlled by the Ca2+/CaM-dependent elongation factor 2 kinase (eEF2K). However, little is known about the dynamics of eEF2K regulation in neurons despite its established role in learning and synaptic plasticity. To explore eEF2K dynamics in depth, we stimulated synaptic activity in mouse primary cortical neurons. We find that synaptic activity results in a rapid, but transient, increase in eEF2K activity that is regulated by a combination of AMPA and NMDA-type glutamate receptors and the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin complex 1 (mTORC1) pathways. We then used computational modeling to test the hypothesis that considering Ca2+-coordinated MEK/ERK, mTORC1, and eEF2k activation is sufficient to describe the observed eEF2K dynamics. Although such a model could partially fit the empirical findings, it also suggested that a crucial positive regulator of eEF2K was also necessary. Through additional modeling and empirical evidence, we demonstrate that AMP kinase (AMPK) is also an important regulator of synaptic activity-driven eEF2K dynamics in neurons. Our combined modeling and experimental findings provide the first evidence that it is necessary to consider the combined interactions of Ca2+ with MEK/ERK, mTORC1, and AMPK to adequately explain eEF2K regulation in neurons. © 2015 Kenney et al.

Yakushevich L.V.,Institute of Cell Biophysics | Krasnobaeva L.A.,Siberian State Medical University
Mathematical Biology and Bioinformatics | Year: 2017

Coding regions (CDS) being an integral part of any gene sequence, play an important role in the process of transcription. One of the tasks associated with the CDS regions, consists in the modeling of the passage of transcription bubbles named also open states or DNA kinks through the coding regions. In this paper, we present a simple and convenient approach to the modeling of the passage. It includes the calculation of the energy profile of the sequence and reducing the initial task to the modeling of the movement of a quasi particle in the field with this energy profile. To illustrate the method, we present the results of the calculations of the trajectories of the DNA kinks moving in the sequence of gene coding interferon alpha 17 (IFNA17) that consists of the three regions: the coding region and the two regions with unknown functional properties. To analyze the kink dynamics, we apply approximation where the DNA parameters are being averaged separately over each of the three regions. In the absences of dissipation, the total kink energy is constant. At the same time the kink velocity is constant only inside each of the regions. In the presence of dissipation, the total kink energy decreases. It is shown that the greater the total initial energy of the kink, the faster the energy decrease. It is suggested that the proposed approach could be useful in finding the ways to govern the movement of transcription bubbles at the first stage of the process of transcription.

Astasheva E.V.,Institute of Theoretical and Experimental Physics | Astashev M.E.,Institute of Cell Biophysics | Kitchigina V.F.,Institute of Theoretical and Experimental Physics
Zhurnal Vysshei Nervnoi Deyatelnosti Imeni I.P. Pavlova | Year: 2017

Oscillations, or rhythms, are necessary for the execution of many cognitive functions as they provide fast and flexible changes in neuronal interactions in different brain structures [Fries, 2005; Womelsdorf et al., 2007]. Until recently insufficient attention was paid to the question of how dif-ferent types of oscillations are synchronized during the processing of the information coming to the brain. In the present work the expressiveness and correlation of rhythmic activity in the theta, alpha and gamma ranges in animals in two behavioral states were analyzed: during quiet wakefulness and during perception of sensory signals. Local field potentials (LFPs) in eight brain structures (cortical and subcortical) were registered. In many areas, an increase of oscillatory activity during the presentation of external signals was revealed. The main result of the present work is the detection of a sharp increase of cross-frequency relations in all oscillatory bands, both in the cortical and subcortical structures during the processing of sensory information. It is supposed that an increase of synchronization of rhythmic activities in different brain areas is necessary for detailed assessment of environmental signals and their registration in the memory system.

Khubutiya M.S.,Sklifosovsky Research Institute for Emergency Medicine | Vagabov A.V.,Sklifosovsky Research Institute for Emergency Medicine | Temnov A.A.,Sklifosovsky Research Institute for Emergency Medicine | Sklifas A.N.,Institute of Cell Biophysics
Cytotherapy | Year: 2014

The purpose of this review is to systematize data from many studies and observations of proliferative, anti-apoptotic and anti-inflammatory effects of mesenchymal stromal cell (MSC) paracrine factors and their biologic effects in models of acute organ injury. © 2014 International Society for Cellular Therapy.

Xie J.,Tsinghua University | Wang C.,Chongqing University | Huang D.-Y.,University of Washington | Zhang Y.,Tsinghua University | And 4 more authors.
Journal of Biomechanics | Year: 2013

The anterior cruciate ligament (ACL) is known to have a poor self-healing ability. In contrast, the medial collateral ligament (MCL) can heal relatively well and restore the joint function. Transforming growth factor-beta1 (TGF-Β1) is considered to be an important chemical mediator in the wound healing of the ligaments. While the role of TGF-Β1-induced expressions of the lysyl oxidases (LOXs) and matrix metalloproteinases (MMPs), which respectively facilitate the extracellular matrix (ECM) repair and degradation, is poorly understood. In this study, we used equibiaxial stretch chamber to mimic mechanical injury of ACL and MCL fibroblasts, and aimed to determine the intrinsic differences between ACL and MCL by characterizing the differential expressions of LOXs and MMPs in response to TGF-Β1 after mechanical injury. By using semi-quantitative PCR, quantitative real-time PCR, western blot and zymography, we found TGF-Β1 induced injured MCL to express more LOXs than injured ACL (up to 1.85-fold in LOX, 2.21-fold in LOXL-1, 1.71-fold in LOXL-2, 2.52-fold in LOXL-3 and 3.32-fold in LOXL-4). Meanwhile, TGF-Β1 induced injured ACL to express more MMPs than injured MCL fibroblasts (up to 2.33-fold in MMP-1, 2.45-fold in MMP-2, 1.89-fold in MMP-3 and 1.50-fold in MMP-12). The further protein results were coincident with the gene expressions above. The different expressions of LOXs and MMPs inferred the intrinsic differences between ACL and MCL, and the intrinsic differences could help to explain their differential healing abilities. © 2012 Elsevier Ltd.

Vekshin N.L.,Institute of Cell Biophysics
Biologicheskie Membrany | Year: 2010

Protomitohondria (PRM) from liver cells of junior (1 month old) and adult (9 month old) rats were isolated using centrifugation and filtration through millipore filters with pore size of 0.10-0.45 μm and characterized by means of photometry and fluorometry. PRM are young mitochondrial organelles, precursors of mature mitochondria (MH), in specialized animal cells. Having hundreds of times smaller volume, PRM do not differ much from MH either in young or in adult rats. However, during maturation of PRM to MH, an increase in the content of flavins and cytochromes is noticeable in young animals. The number of PRM of various sizes in young and adult rats differs. In addition, there are strong differences in the intensity of fluorescence of the probe ANS in PRM and MH of younger and older animals, suggesting a different number of binding sites. The obtained data suggest that the total transformation of PRM to MH in cells of young animals takes place, similarly with the transformation in cells of adult rats.

Lunin S.M.,Institute of Cell Biophysics | Novoselova E.G.,Institute of Cell Biophysics
Expert Opinion on Therapeutic Targets | Year: 2010

Importance of the field: Inflammatory diseases are characterized by severe immune imbalances, leading to excessive or inappropriate release of mediators, which, in turn, result in massive damage to organs and systems. Effective means to control inappropriate immune reactions are often life-critical needs. Available data on the role of thymus-derived hormones in inflammation show their great potential. Areas covered in this review: The review aims to systematize information for the last two decades on immune system regulation by thymic peptide hormones, with a primary focus on the role of these hormones in the systemic inflammatory response and inflammatory diseases. Anti-inflammatory potential of three thymic hormones thymulin, thymosin-alpha, and thymopoietin is discussed, reviewing recently published clinical and experimental studies. What the reader will gain: Our analysis revealed the regulation of inflammatory processes via thymic hormones that could be prospective for therapeutic application. This regulation may be mediated through thymic hormone effects on peripheral immune cell activities and bidirectional coupling between thymic hormones and the hypothalamicpituitaryadrenal axis. Take-home message: In view of the role of thymic hormones in immune and neuroendocrine systems, they could be suitable as therapeutic agents for inflammation. © 2010 Informa UK Ltd.

Lunin S.M.,Institute of Cell Biophysics | Glushkova O.V.,Institute of Cell Biophysics | Khrenov M.O.,Institute of Cell Biophysics | Novoselova T.V.,Institute of Cell Biophysics | And 3 more authors.
Immunobiology | Year: 2013

Modulation of autoimmune inflammation by the thymic peptides thymulin and thymopentin was studied in mice with acute experimental autoimmune encephalomyelitis (EAE), which resembles multiple sclerosis in humans. EAE was induced in NZW mice by a single immunisation with myelin basic protein coupled with adjuvants. Visible signs of pathology appeared on days 12-14 after the immunisation, peaked on days 20-25, were retained up to day 45, and then reverted. A biphasic cytokine response was also detected. In the " early" phase, which started at day 35, increased levels of interferon-gamma and interleukin-6 in the blood were observed; during the " delayed" phase, which started at day 48, the levels of plasma interleukin-17 and tumour necrosis factor-alpha were also raised. In addition, the phosphorylation of NF-kappaB signalling proteins and the production of heat shock protein Hsp72 were significantly increased in splenic lymphocytes from EAE-bearing mice. When applied intraperitoneally every other day for 30 days, either thymulin or thymopentin (15. μg per 100. g of body weight) significantly reduced the disease severity compared to untreated EAE mice. The effect of thymulin but not thymopentin remained after its withdrawal. Thymulin reduced the cytokine response in both the early and the delayed phases, whereas thymopentin only reduced the " early phase cytokines" (IL-6 and interferon-gamma). Both peptides significantly reduced the level of phosphorylation of the NF-kappaB signalling protein IKK and the production of Hsp72 protein. The data presented here indicate the presence of time-dependent immune responses in EAE-bearing mice, which may be associated with the Th1 and Th17 subpopulations of T-cells. Thymulin and thymopentin demonstrated different patterns of activity, most likely via mechanisms involved in NF-kappa B signalling and Hsp72 expression. © 2012 Elsevier GmbH.

Frolova M.S.,Institute of Cell Biophysics | Vekshin N.L.,Institute of Cell Biophysics
Journal of Fluorescence | Year: 2014

It is known that one of the reasons, leading to the development of neuromuscular diseases, including Parkinson's disease, is damage of the mitochondrial NADH-dehydrogenase. Perhaps, it happens when NADH-dehydrogenase loses connection with its coenzyme - flavine mononucleotide (FMN) that occurs at various influences on the enzyme. Previously, we have developed a method, based on fluorescence spectroscopy, to monitor the rate of exit of FMN from isolated mitochondria to solution. Also, we obtained the data that this process is blocked by the enzyme substrate - NADH or by the product - NAD. Recently, we found that this process is strongly blocked by adenine analogs of NAD, contained phosphates: ATP, ADP, and AMP. Adenosine phosphates are able to stabilize the FMN molecule in NADH-dehydrogenase. Using fluorescence spectroscopy and photocolorimetry, we have tested also other natural purine compounds - cAMP, cGMP, GMP, GDP, GTP, IMP, inosine, guanine, and caffeine. It is found that such derivatives of guanine as GMP, GDP, and GTP can prevent the release of FMN into solution. Guanine, cGMP, cAMP and caffeine did not prevent this process. The obtained data allow understand the mechanism of mitochondrial diseases, involving damage of mitochondrial NADH-dehydrogenase, and may help in development of medicines for treatment of these diseases. © 2014 Springer Science+Business Media New York.

Novoselova E.G.,Institute of Cell Biophysics | Lunin S.M.,Institute of Cell Biophysics | Khrenov M.O.,Institute of Cell Biophysics | Parfenyuk S.B.,Institute of Cell Biophysics | And 3 more authors.
Immunobiology | Year: 2015

To explore the effect of the spaceflight environment on immunity in animals, C57/BL6 mice flown on a 30-day space high-orbit satellite mission (BION-M1) were analyzed. Cytokine response in mice was measured in tandem with the following parameters: the synthesis of inducible forms of the heat shock proteins HSP72 and HSP90α; activity of the NF-κB, IFR3, and SAPK/JNK signalling pathways; and TLR4 expression. In addition, apoptosis in the thymus was measured by caspase-3 and ph-p53/p53 ratio testing. In response to flight environment exposure, mice had a reduction in spleen and thymus masses and decreased splenic and thymic lymphocyte counts. Plasma concentration of IL-6 and IFN-γ but not TNF-α was decreased in C57BL6 mice. The NF-κB activity in splenic lymphocytes through the canonical pathway involving IκB degradation was significantly increased at 12. h after landing. One week after landing, however, the activity of NF-κB was markedly decreased below even the control values. Non-canonical NF-κB activity increased during the whole observation period. The activities of SAPK/JNK and IRF-3 were invariable at 12. h but significantly increased 7 days after landing. The expression of Hsp72 and Hsp90α was somewhat increased 12. h (Hsp72) and 7 days (Hsp90α). TLR4 expression in splenic cells was significantly increased only at 12. h, returning to normal 7 days after landing. To assess the apoptosis in thymus lymphocytes, caspase-3 and levels of p53 protein along with its phosphorylated form were measured in thymic lymphocytes. The results indicated that the high-orbit spaceflight environment caused an increase in the level of p53 but more notably in the activated, phosphorylated form of the p53 protein. The calculated ratio of the active to inactive forms of the protein (ph-53/p53) 12. h after landing increased by more than twofold, indicating the apparent induction of apoptosis in thymus cells. Interestingly, 7 days after the landing, this ratio was not restored, but rather increased: the specified ratio was four times higher compared to the ground-based control. Measurements of caspase-3 in thymic cells indicated more expressive increase in apoptosis. Taken together, the results of the present study indicate that spaceflight induces an imbalance in the immunity of mice, showing variation in signalling, apoptosis and stress response that are not restored by 7 days after landing. These changes are distinguished from classic stress-related alterations usually caused by conventional stressors. © 2014 Elsevier GmbH.

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