


Vol 10, No 1 (2016)
- Year: 2016
- Articles: 9
- URL: https://journal-vniispk.ru/1990-7478/issue/view/13260
Reviews
Intercellular signaling in microbial world: A panoramic view
Abstract
In the microbial world, there are various communicative interactions via secreted chemical intermediates. Some of these interactions can be considered as signaling, as they trigger specific physiological responses by modulating transcription of cognate gens. This review briefly presents the history of the studies on microbial intercellular signaling along with current concepts of the signaling mechanisms of yeast mating, as well as of intraand interspecies communication in bacteria.



Articles
Induction of cyclosporine-sensitive mitochondrial permeability transition pore by substrates forming acetyl-CoA under normal conditions and in type 2 diabetes
Abstract
Oxidation of pyruvate and palmitoylcarnitine in mitochondria is accompanied by the formation of acetyl-CoA, with its possible participation in the acetylation of various proteins and enzymes that may lead to the inhibition of their functions. This paper studies the effect of the excess of these substrates on respiration and induction of mitochondrial permeability transition pore (MPTP) in mitochondria and liver homogenates of healthy, obese, and type 2 diabetic (T2D) rats and mice. Both substrates produced a reversible inhibition of respiration and induced the opening of MPTP sensitive to cyclosporin A. Induction of MPTP in mitochondria was further activated by calcium ions and inhibited by the NO donor SNAP and NAD–a coenzyme and activator of deacetylation reactions. In obese and T2D animals, the opening of MPTP was stimulated by lower concentrations of L-palmitoylcarnitine than in healthy animals. In these pathologies, an activation effect on the MPTP induction was produced by ammonium ions, in the presence of which the concentration of L-palmitoylcarnitine required for the pore opening was reduced more than twofold. In liver homogenates, an added arginine reduced the probability of the MPTP formation. Analysis of mathematical models has shown that, due to the inhibition of pyruvate dehydrogenase kinase (PDK) by pyruvate, phosphorylation of pyruvate dehydrogenase (PDH) is strongly reduced, and this makes it possible to produce acetyl CoA in a wide range of pyruvate concentrations. The data obtained show that excess substrates that produce acetyl-CoA increase the probability of the MPTP opening, especially in pathologies associated with obesity and T2D. The ability of NO and NAD to inhibit MPTP indicates the participation of phosphorylation and acetylation/deacetylation reactions in this process.



Induction of calcium-dependent nonspecific permeability of the inner membrane in liver mitochondria of mammals and birds: A comparative study
Abstract
The kinetics of the processes accompanying the induction of Ca2+-dependent permeability (pore opening) of the inner membrane—swelling of organelles and Ca2+ release from the matrix—was studied in isolated liver mitochondria of mammals (mice, rats, and rabbits) and birds (pigeons and guinea fowls). It was found that the mitochondria of rats, pigeons, and guinea fowls of the gray-speckled population (GSP) are similar in terms of respiration and oxidative ATP synthesis, whereas mitochondria of rabbits exhibit a greater degree of coupling of respiration and ATP synthesis, and mitochondria of mice and Zagorskaya White breed (ZWB) guinea fowls, a lower degree of coupling. It was established that mammalian mitochondria energized by succinate oxidation and incubated with 1 mM of inorganic phosphate are able to swell upon the addition of 125 nmol of CaCl2 per 1 mg protein. Under these conditions, mitochondria of GSP and ZWB guinea fowls and pigeons are capable of swelling upon addition of at least 875, 875 and 1000 nmol of CaCl2 per 1 mg protein, respectively. Cyclosporin A (CsA, 1 μM) inhibits mitochondrial swelling. It was shown that mitochondria of mammalians and guinea fowls but not of pigeons are able to effectively absorb and retain Ca2+ in the matrix. Calcium retention capacity of mitochondria from rats, mice, rabbits, GSP, and ZWB guinea fowls were, respectively, 70, 57, 38, 844 and 793 nmol of CaCl2 per 1 mg of protein. In the presence of an oxidizing agent tert-butylhydroperoxide (TBH), the induction of the Ca2+-dependent pore in the mitochondria was observed upon addition of CaCl2 in substantially smaller quantities. TBH was most effective in the case of rabbit mitochondria and had the lowest efficiency in the case of guinea fowl and pigeon mitochondria.



Mitochondria as a target for neuroprotection
Abstract
Despite all the efforts of modern medical and biomedical sciences, the effective therapeutic treatments that would restore the brain functions lost after stroke have not been found yet. At the same time, experimental preclinical studies revealed an arsenal of effectors having potential for clinical applications. Identification of the key signaling pathways, both damaging and protective, can accelerate the development and implementation of new effective neuroprotectors. One of the key elements of these pathways is mitochondrion. In this context, we studied various therapeutic approaches to the treatment and prevention of cerebral ischemia, which are aimed at modulation of mitochondrial functions. The spectrum of tested neuroprotectors included antioxidants, uncouplers of respiration and phosphorylation, as well as ischemic, remote, and pharmacological preconditioning. Their efficacy and therapeutic windows were compared and the possibility of combining different methods in order to maximize their efficiency was considered.



Product fermented by Lactobacilli induces changes in intracellular calcium dynamics in rat brain neurons
Abstract
In this work we investigated the effect of concentrated metabolic products of lactobacilli (PP) on the dynamics of intracellular calcium concentration ([Ca2+]i) in rat brain neurons. [Ca2+]i was recorded using a fluorescent probe Fura-2 and a ratiometric Ca2+ imaging. It was found that PP increased [Ca2+]i, stimulating the intracellular signaling mechanisms. In these processes the activation of ryanodine receptors and protein kinase C are involved at least partially. Continuous application of PP stimulated a sustained release of Ca2+ from the endoplasmic reticulum and subsequent entry of Ca2+ into the cell. Given that PP is able to stimulate circulation and neurogenesis and is involved in calcium homeostasis in nerve cells in the brain, PP can be regarded as a product for the improvement of psychological parameters and cognitive functions of the brain.



Two populations of pluripotent stem cells in planarians Girardia tigrina
Abstract
The positional differences in the regenerative capability of individual body parts of the planarian Girardia (Dugesia) tigrina were analyzed. The paper shows the significance of the size and positional differences of individual fragments of planarians for their regenerative capabilities, as well as the fundamental difference in the mechanisms of the head and tail blastema formation. A scheme of regeneration that includes two populations of pluripotent stem cells called neoblasts is suggested. The two populations of neoblasts differ in their role and distribution along the planarian body. Specifically, the population of neoblasts involved in the formation of any blastema migrates to the nearest blastema, and the population participating only in the creation of the head blastema migrates along the planarian body, following the gradient of biomass of the damaged axons arising after the amputation of the head end. The maximal size of the head blastema was found in the fragment obtained after cutting off the head fragment at the eye level, and the maximal portion of all pluripotent stem cells migrating into two blastemas was found in the fragment obtained by cutting the planarian above the mouth, followed by cutting off the head fragment at the eye level.



Insulin induces Ca2+ oscillations in white fat adipocytes via PI3K and PLC
Abstract
Adipocytes of white adipose tissue are the cells maintaining glucose homeostasis in an organism, which is controlled by insulin. Insulin stimulates the translocation of glucose transporter GLUT4 from the cytosol into the cell membrane, as well as glucose transport and utilization in these cells. Here we show that insulin-induced [Ca2+]i oscillations are supported by the two signaling pathways involving: (1) phosphoinositide 3-kinase (PI3K), protein kinase B (Akt/PKB), endothelial NO synthase (eNOS), nitric oxide (NO), and ryanodine receptor (RyR) and (2) phospholipase C (PLC) and inositol 3-phosphate receptor (IP3R). Thus, the PI3K Akt/PKB signaling pathway initiates not only metabolic but also Ca2+-signaling pathways in response to insulin.



The role of the intra- and extracellular protons in the photosynthetic response induced by the variation potential in pea seedlings
Abstract
Local burning induces generation and propagation of variation potential (VP) in higher plants. VP induces transient inactivation of photosynthesis, which is possibly connected with proton signal in plant cell. Analysis of the role of changes in intracellular and extracellular pH in the VP-induced photosynthetic response in pea seedlings was the aim of this work. It was shown that local burning induced VP propagation, which was accompanied with a decrease of intracellular pH and increase of extracellular pH. VP induced photosynthesis inactivation that included an increase in the nonphotochemical fluorescence quenching and a decrease in the CO2 assimilation rate. Analysis of photosynthetic responses under control and low external CO2 concentration and changes in pH showed that there were two components in the responses. The first component appeared as a fast decrease of the CO2 assimilation and increase of nonphotochemical quenching. It depended on the activity of the dark stage of photosynthesis and was connected with apoplast alkalization. The second component was presented as a slow increase of nonphotochemical quenching. It weakly depended on a dark stage and was connected with a decrease of intracellular pH.



Actovegin protects human neuroblastoma cells SK-N-SH from apoptosis induced by hydrogen peroxide through the PI3K and p38 MAPK signaling pathways
Abstract
Neurodegenerative disorders of the central nervous system (CNS) are associated with an increased production of hydrogen peroxide (H2O2), which is an inducer of apoptosis in various cell types including CNS. Previously it was shown that actovegin (deproteinized calf blood hemodialysate) reduces neuronal apoptosis, but the mechanism of its protective action is still poorly understood. The effect of actovegin on the apoptosis of SK-N-SH human neuroblastoma cells was studied in the present work. The role of different intracellular signaling pathways involving mitogen-activated protein kinases was analyzed using selective inhibitors. Our data show that the signaling pathways involving p38 MAPK and PI3K play the key role in the protective effect of actovegin against hydrogen peroxide-induced apoptosis in SK-N-SH cells.


