


Vol 40, No 3 (2023)
- Year: 2023
- Articles: 6
- URL: https://journals.rcsi.science/0233-4755/issue/view/6757
Articles
BAR Domain Proteins As Putative Regulators of the Protein Liquid Phase in Nerve Terminals in the Central Nervous System
Abstract
BAR proteins are key components of the synaptic vesicle cycle in nerve terminals. They participate in the regulation of neurotransmitter release during the fusion of synaptic vesicles with the presynaptic membrane and synaptic vesicle recycling. Localization of these proteins at sites of liquid–liquid phase separation in nerve terminals suggests additional functions of these molecules. In the current review, we discuss the tasks of BAR proteins at different stages of the secretory cycle, including their putative role in liquid–liquid phase transitions in nerve terminals during synaptic activity. We suggest that BAR proteins, along with their established functions in exo- and endocytosis, play crucial roles in the organization of the reserve pool of synaptic vesicles and at the intermediate stages of the vesicle cycle.



Effects of Plant Acclimation on Electron Transport in Chloroplast Membranes of Cucumis sativus and Cucumis melo
Abstract
In this work, we have studied photosynthetic electron transport in chloroplasts of two “contrasting” species of Cucumis genus, the shade-tolerant species Cucumis sativus (cucumber) and the light-loving species Cucumis melo (melon). Plants were acclimated to moderate (50–125 μmole photons m−2 s−1) or high light (850– 1000 μmole photons m−2 s−1). Parameters of a fast induction of chlorophyll a fluorescence, emitted from photosystem 2 (PS2), were determined using a conventional OJIP test. For monitoring the turnover of photosystem 1 (PS1) reaction centers P+700, we used electron paramagnetic resonance. The shade-tolerant (C. sativus) and light-loving (C. melo) species, acclimation to high or low light irradiation, revealed substantial difference in their response to variations of light intensity. Photosynthetic activity of shade-tolerant species C. sativus revealed higher sensitivity to light intensity during acclimation as compared to C. melo. In the course of the long-term acclimation (more than 2 months) of С. sativum to high light (≥ 500 μmole photons m−2 m−1), a photochemical activity of PS2 decreased. This was not the case, however, for leaves of C. melo. In С. sativus leaves, a decrease in photochemical activity of PS2 caused by acclimation to high light was reversible, demonstrating the recovery after the attenuation of irradiation intensity. Plants of both species acclimated to high and low light also revealed significant differences in the two-phase kinetics of redox transients. In the leaves of plants acclimated to strong light, we observed a lag-phase in the kinetics of photooxidation that could be attributed to cyclic electron transport (CET) around PS1. The ratio of the signals induced by white light and far-red light (707 nm) was higher in plants acclimated to strong light. This effect can be explained by the enhancement of CET and optimization of the energy balance at excess of light, protecting plants from oxidative stress. The data obtained are discussed in the context of the problem of photosynthesis optimization upon fluctuations of light intensity.



Model of a Molecular Proton Sensor in Taste Cells
Abstract
Otopetrins represents a group of membrane proteins that function as proton-selective ion channels. Existing evidence indicates that Otop1, the eponym of the family, is a likely molecular sensor of protons involved in detecting acid stimuli in taste cells of type III. Acid stimuli is believed to initiate an inward current carried by protons through receptive apical membrane to depolarize a type III cell and trigger a train of action potentials driving afferent neurotransmission. While many details of this rather complicated process have not been uncovered yet, mathematical modelling could provide a sufficient insight into sour transduction. Here we present a mathematical model for describing dynamic and transport properties of Otop1 channel. The elaborated model appropriately describes proton currents through Otop1 under different conditions, and it could be employed for further modeling of sour responses of taste cells.



Activation of the Cannabinoid Receptors Suppresses Hyperexcitation of Rat Hippocampal Neuronal Networks in vitro
Abstract
Cannabinoid receptors (CBRs) play a key role in various physiological processes, including neurogenesis, synaptic plasticity, immune modulation, cell apoptosis, metabolism regulation, cardiovascular and reproductive systems activity. Since activation of CBRs suppresses hyperexcitation and protect cells from death, their modulation may have therapeutic prospects in the treatment of such pathologies of the nervous system as mental disorders, epilepsy, Parkinson’s and Huntington’s disease, multiple sclerosis, spinal cord and brain injuries. This paper presents experimental data on the effects of the cannabinoid receptor agonist WIN 55,212-2 on the induced oscillations of intracellular Ca2+ concentration ([Ca2+]i) in two in vitro models of epileptiform activity. To study the neuroprotective properties of WIN 55,212-2, hyperexcitation was induced by the application of a GABA(A) receptor antagonist, bicuculline, or depolarizing doses of ammonium chloride. As experiments have shown, WIN 55,212-2 at a concentration of 100 nM and above significantly suppresses the [Ca2+]i oscillation frequency and reduces the basal [Ca2+]i level. At the same time, the amplitude of calcium oscillations also decreased in the presence of the agonist. WIN 55,212-2 at a concentration of 5 μM suppressed NH4Cl-induced [Ca2+]i oscillations in all neurons but caused a transient biphasic increase in the basal [Ca2+]i level in 20% of astrocytes. Thus, in this work, using various models of hyperexcitation of neuronal networks, we have demonstrated the potential antiepileptic effect of the cannabinoid receptor agonist WIN 55,212-2.



Mixed Cationic Liposomes Based on L-Amino Acids As Efficient Delivery Systems of Therapeutic Molecules into Cells
Abstract
This work aimed to produce mixed liposomes based on natural amino acids as vehicles for delivery of anticancer drugs and nucleic acids. Liposomes were formed from cationic lipids based on L-alanine and L-serine, a kerase-forming lipid based on L-ornithine, and phospholipids phosphatidylcholine (PC) or 1,2-dioleoyl- sn-glycero-3-phosphoethanolamine (DOPE). For the developed agents, particle size, zeta potential, and stability were determined, and the biological activity was studied on the MCF-7 and HEK 293 cell lines. Liposomes based on L-serine demonstrated the ability to accumulate in the endoplasmic reticulum of cells within 1 h, and their transfection activity significantly exceeded that of the commercial drug Lipofectamine- 2000. At the same time, the proposed system had a slight toxic effect (IC50, 0.475 mg/mL and the safe working concentration, 0.24 mg/mL).



Interaction of Mesenchymal Stromal Cells with Primary 5XFAD Mice Hippocampus Culture Depending on Cocultivation Method
Abstract
In this work we studied the mutual influence of multipotent mesenchymal stromal cells (MMSC) isolated from Wharton’s jelly of human umbilical cord and primary culture of hippocampal cells obtained from transgenic mice 5XFAD, used as an animal model of inherited form of Alzheimer’s disease (AD). Experimental protocols included both direct and indirect co-cultivation of MMSCs with hippocampal cells from transgenic animals. It was shown that in the conditions of indirect co-culture, the aggressive environment of cultured transgenic cells significantly decreases the survival rate and adhesiveness of MMSCs. However, preliminary priming of MMSCs with proteins YB-1 and HSP70 improved the survival and adhesive properties of MMSCs. It was also found that the interactions of MMSCs with cultured hippocampal cells depend on cell culture age. Old cultures of transgenic cells induced differentiation of MMSC into astrocytes, both during direct and indirect co-cultivation. In contrast, in young cultures of transgenic cells, during contact co-cultivation, MMSCs played the role of specific strands that promoted clustering of hippocampal cells in the culture and the formation of neurospheres. The interaction between MMSCs and neural cells occurred through gap junctions and nanotubes. Our findings expand the understanding of interactions between MMSCs and recipient cells, which allows us to revise the conditions of cellular transplantation therapy for pathological processes in the brain of AD patients.


