卷 69, 编号 1 (2024)

This study is a continuation of our previous research aimed at investigating changes in the pools of amino acids in the myocardium of the ground squirrel during winter torpor. Neurochemical profiles of amino acids and the secondary metabolites (taurine, phosphoserine, and cysteic acid) were explored in the neocortex of the ground squirrel at different stages of torpor: in the beginning of torpor (2–3 days) and during prolonged torpor (9–10 days), as well as during short-term winter arousal (winter activity, euthermia). Reduced excitatory neurotransmitter levels (glutamate by 7% and 14%; aspartate by 25% and 52% in a coordinated manner and the increased level of GABA, the main transmission inhibitor (by 50% and 67%) were observed from the onset of the torpor entry and at the end of the torpor arousal, respectively. Alanine, which was formed in negligible amounts in the neocortex in the summer season, increased at the initial stage of hibernation and after multiday torpor bout (by 98% and 126%, respectively), indicating a partial switch to anaerobic glycolysis. Short-term inter-bout euthermia returned levels of these substances back to normal. The behavior of glutamate and aspartate, the anaplerotic substrates, that supported cycling of the tricarboxylic acid cycle during torpor and winter activity periods was like their responses in the myocardium, though differed quantitatively. The responses of the neuromodulators such as glycine, threonine, and lysine differed radically when compared to their responses in the myocardium. No changes in taurine and phosphoserine pools were detected, but the level of cysteic acid decreased compared to the summer control from 0.51 ± 0.06 μmol/g to 0.07 ± 0.01 μmol/g at the end of torpor, while during winter euthermia it became 2 times lower than the summer level. Our data suggest that metabolic pathways, involving anaplerotic amino acids of the neocortex, are more active than the myocardium during winter torpor, while the pools of neuromodulators that regulate inhibition processes, increase.

Studying the voltage-gated calcium channels sheds light on the formation of systems responsible for the coupling of sensors and actuators in a living cell. A homologue of 2090 aa lUNKth in the Trichoplax sp. H2 scaffold and an incomplete protein of 1510 aa lUNKth in the Trichoplax adhaerens scaffold were identified on the basis of the data on the voltage-gated calcium channel TCav3 (2063 aa) from the Trichoplax adhaerens cells. The incomplete hypothetical protein is annotated as Cav3-channel. An EEDD selective filter was found for all 3 proteins and the calcium channel core structure consisting of 24 trans-membrane α-helices was reconstructed. However, the studied proteins demonstrated significant variations in their cytoplasmic domains that indicates the different specialization of Cav3-channels in the signal transduction. So part of the AID motive (alpha-interacting domain) and the adjacent potential sensor from the annotated channel have homologies in 25 species of bony fish, and the corresponding region from both other channels in 41 species of bony fish and in 4 species of snakes was found. Significantly, a highly conserved IIS1-S2 loop with the IEHHNQP sequence was identified lower from the AID motif of bony fish, like in Trichoplax, while the homologous IEHHEQP sequence was revealed in snakes, which differs in the negative residue of glutamic acid that is also present in the corresponding proteins of the rat and human. A modular mechanism for the evolution of Cav3-channels by insertions and merging of protein domains that perform various regulatory functions is suggested based on the analysis of primary transcripts and mature proteins.

Plant-based protein isolates are common food ingredients. Differential scanning calorimetry is used to forecast functional properties of these isolates as well as to evaluate the propensity of these isolates for bioplastic formation through heat-induced formation of intermolecular disulfide, hydrophobic, and other types of bonds. In this work, differential scanning calorimetry was employed in the study of a suspension containing soy protein isolate and glycerol. It was shown that heat release occurred upon heating the isolate in the presence of glycerol. Preheating-induced denaturation of soy proteins in aqueous solution (95°С, 30 min) made the observed heat more exothermic, whereas exothermic reaction was not observed during enzymatic hydrolysis of the protein. Since adding β-mercaptoethanol to soy protein isolate had no effect on the observed exothermic process, this chemical compound could not contribute to formation of new disulfide bonds. Thus, bioplastic formation using soy protein isolate occurs independently of the formation of new disulfide bonds, and differential scanning calorimetry can be used to assess protein solubility.

Mitochondria are involved in the development of diseases with different etiologies. The use of drugs which can enhance the functional state of mitochondria may turn into a promising therapeutic approach to diseases with different etiologies. Astaxanthin, a keto-carotenoid (xanthophyll) predominantly of marine origin, shows both lipophilic and hydrophilic properties and can penetrate the cell membrane to localize to mitochondria where it prevents mitochondrial dysfunction. This study examined the effect of astaxanthin on the functional state of rat brain mitochondria, investigated the changes in mitochondrial dynamics and mitophagy under isoproterenol-induced injury. In the presence of astaxanthin, mitochondria were more resistant to Ca2+-induced opening of a nonspecific pore, and the activity of complexes I, IV and V of the respiratory chain increased. Moreover, the presence of astaxanthin led to altered mitochondrial fission and fusion as well as mitophagy, in isoproterenol-induced mitochondrial dysfunction. This presumably increased the quantity of rat brain mitochondria and enhanced their functional state. Astaxanthin can be considered as a mitochondria-targeted agent in therapy in pathological conditions associated with oxidative damage and mitochondrial dysfunction caused by acute heart failure. Astaxanthin as a dietary supplement has the potential to provide antioxidant protection to cells in cardiovascular disease.

A number of our studies have shown that low-frequency (LF) oscillations in the functional parameters of the oxygen transport system are stable and synchronized with one another. The literature presents a large number of examples of LF oscillations in various functional parameters that are directly or indirectly related to energy metabolism. In parallel, artificially induced damped and constant spontaneous oscillations related to energy produced by the mitochondria over a range of LF frequencies have been studied for more than 40 years. A parameter study is therefore needed to find the connection between the oscillation amplitudes and the physical characteristics both of the oxygen transport system and mitochondria that operate on common LF range (0.003–0.03 Hz). We believe the nature of all these oscillation amplitudes to be affected by the periodic dynamics of energy dissipation in mitochondria that form an interconnected network. The process of creating these oscillations occurs in two phases. In the 1st phase, the amount of Са2+ entering the mitochondria exceeds the amount of Са2+ released by mitochondria thereby promoting an increase in oxidative phosphorylation efficiency. In the 2nd phase, Са2+ efflux from mitochondria prevails over Са2+ influx and is accompanied by inhibition of oxidative phosphorylation. The oscillations remain stable and spontaneous and arise from an “autocatalytic” interaction based on feedback mechanisms. The inertia of the processes of a full cycle (1st and 2nd phases) that lasts 1–3 minutes may be due to the capacity of the phosphate buffer of mitochondria. The structural basis for synchronizing oscillations at the tissue level may be mitochondrial networks of excitable tissues. Synchronization at the organism level between mitochondrial oscillations and fluctuations in parameters associated with energy metabolism can be achieved through a system of tunnel nanotubes.

Electron paramagnetic resonance (EPR) spectroscopy was used to determine the content of nitric oxide (NO) and copper in the hippocampus of healthy rats and rat models of ischemia. The rat model of ischemia was established via both carotid arteries ligation and ligation of the carotid arteries with subsequent withdrawal of a 3 ml of blood from the common carotid artery. The EPR signals of the (DETC)2-Fe2+-NO and Cu(DETC)2 complexes were recorded. The NO level in the hippocampus showed a significantly drop by an average of 28% one day after modeling ischemic stroke caused by carotid artery ligation and by 56% in the rat model of ischemia established via ligation of the carotid arteries with subsequent withdrawal of a 3 ml of blood from the common carotid artery. The copper content decreased significantly in the hippocampus by an average of 20% one day after modeling ischemia by ligation of the carotid arteries and our findings indicate that the copper content tends to decrease in the rat model of ischemia established via ligation of the carotid arteries with subsequent withdrawal of blood. High variability couldn’t tell us if there was a significant difference between groups, though. Thus, brain hypoxia of rats subjected to carotid arteries ligation is accompanied not only by a decrease in NO production in the hippocampus, but also by signs of a weakening of the antioxidant system, thus, worsening conditions for the maintenance of homeostasis.

Hafnium is a promising element as contrast agent for diagnostic and therapeutic radiology. Currently there is no suitable hafnium drugs with renal excretion, which can be used in radiology. In this work two new hafnium complexes with nitrilotriacetic acid (Hf-NTA) and 1,2-diaminocyclohexanetetraacetic acid (Hf-CDTA) were synthesized and studied for acute toxicity and biodistribution. Inorganic chemistry methods were used for Hf-NTA and Hf-CDTA synthesis. Acute toxicity was studied in female mice C57Bl/6. Biodistribution and contrast properties studies of Hf-CDTA were made in vivo with micro-CT. Mice with transplanted subcutaneous mammary adenocarcinoma Ca755 were used for the study. Median lethal dose (LD50) of Hf-CDTA was assessed as 408 ± 64 mg Hf/kg and of Hf-NTA less than 120 mg Hf/kg. CT imaging of mice intravenously injected with Hf-CDTA confirmed its renal excretion and contrast capability. CT imaging of tumor region with single intratumoral administration of Hf-CDTA showed promising hafnium concentration and retention in tumor for use in contrast enhanced radiotherapy. Hf-CDTA showed acceptable toxicity and biodistribution in mice with subcutaneous tumors for biomedical application in radiology and radiotherapy. For diagnostic clinical application Hf-CDTA formulation must be improved to increase water solubility and decrease toxicity. Hf-NTA appeared to be unacceptably toxic for radiological application.

Based on cerebrospinal fluid flow dynamic parameters, an original formula for assessing pathology of the spinal motion segments of the vertebra is given. In this paper, graphs are used to clearly show changes in pathology depending on the depth of trauma. The data collected can be useful for computed tomography and magnetic resonance imaging technicians, who still describe pathology in a simple way.