Biochemistry (Moscow)最新文献

{"title":"Accumulation of Li⁺ Ions Triggers Changes in <i>FOS</i>, <i>JUN</i>, <i>EGR1</i>, and <i>MYC</i> Transcription in the LiCl-Treated Human Umbilical Vein Endothelial Cells (HUVEC).","authors":"Olga E Kvitko, Dmitrii A Fedorov, Svetlana V Sidorenko, Olga D Lopina, Elizaveta A Klimanova","doi":"10.1134/S0006297924100146","DOIUrl":"https://doi.org/10.1134/S0006297924100146","url":null,"abstract":"<p><p>Changes in intracellular concentrations of Na⁺ and K⁺ are shown to alter gene expression. Another monovalent cation, Li⁺, is well known as a medicine for treatment of psychiatric disorders, but mechanism of its action is obscure. Thus, it is important to evaluate the effect of Li⁺ on gene expression in endothelial cells. Here we studied influence of the increased intracellular Na⁺ or Li⁺ concentrations on transcription of Na⁺_i/K⁺_i-sensitive genes. Treatment of the human endothelial cells (HUVEC) with LiCl for 1.5 h resulted in accumulation of Li⁺ in the cells. This was followed by increase in the <i>FOS</i> and <i>EGR1</i> mRNAs levels and decrease in the <i>JUN</i> and <i>MYC</i> mRNA levels. Treatment of HUVEC with the Na⁺-ionophore monensin led to accumulation of Na⁺ and loss of K⁺ ions. However, monensin had no significant effect on gene expression. Incubation of HUVEC with elevated extracellular NaCl concentration increased intracellular K⁺ concentration and transcription of the <i>ATF3</i> gene, while transcription of the <i>JUN</i> gene decreased. These results indicate that Na⁺ and Li⁺ ions have different effects on the gene expression profile in the cells that is likely associated with the fact that they affect differently the intracellular monovalent cations ratio.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1844-1850"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Study of Spectral and Functional Properties of Wild Type and Double Mutant H(L173)L/I(L177)H Reaction Centers of the Purple Bacterium <i>Cereibacter sphaeroides</i>.","authors":"Tatiana Yu Fufina, Alexey A Zabelin, Ravil A Khatypov, Anton M Khristin, Anatoly Ya Shkuropatov, Lyudmila G Vasilieva","doi":"10.1134/S0006297924100109","DOIUrl":"https://doi.org/10.1134/S0006297924100109","url":null,"abstract":"<p><p>Previously, we found that in the reaction center (RC) of the purple bacterium <i>Cereibacter sphaeroides</i>, formation of heterodimeric primary electron donor (P) caused by the substitution of His-L173 by Leu, was compensated by the second mutation Ile-L177 - His. Significant changes in the spectral properties, pigment composition, and redox potential of P observed in the H(L173)L RC, are restored to the corresponding characteristics of the native RC in the RC H(L173)L/I(L177)H, with the difference that the energy of the long-wavelength Q_Y optical transition of P increases significantly (by ~75 meV). In this work, it was shown using light-induced difference FTIR spectroscopy that the homodimeric structure of P is preserved in the RC with double mutation with partially altered electronic properties: electronic coupling in the radical-cation of the P⁺ dimer is weakened and localization of the positive charge on one of its halves is increased. Results of the study of the triple mutant RC, H(L173)L/I(L177)H/F(M197)H, are consistent with the assumption that the observed changes in the P⁺ electronic structure, as well as considerable blue shift of the Q_Y P absorption band in the RC H(L173)L/I(L177)H, are associated with modification of the spatial position and/or geometry of P. Using femtosecond transient absorption spectroscopy, it was shown that the mutant H(L173)L/I(L177)H RC retains a sequence of reactions P* → P⁺B_A^- → P⁺H_A^- → P⁺Q_A^- with electron transfer rates and the quantum yield of the final state P⁺Q_A^- close to those observed in the wild-type RC (P* is the singlet-excited state of P; B_A, H_A, and Q_A are molecules of bacteriochlorophyll, bacteriopheophytin, and ubiquinone in the active A-branch of cofactors, respectively). The obtained results, together with the previously published data for the RC with symmetrical double mutation H(M202)L/I(M206)H, demonstrate that by introducing additional point amino acid substitutions, photochemical activity of the isolated RC from <i>C. sphaeroides</i> could be maintained at a high level even in the absence of important structural elements - axial histidine ligands of the primary electron donor P.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1789-1802"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetics of Electron Transfer between Redox Cofactors in Photosystem I Measured by High-Frequency EPR Spectroscopy.","authors":"Andrey A Sukhanov, Georgy E Milanovsky, Liya A Vitukhnovskaya, Mahir D Mamedov, Kev M Salikhov, Alexey Yu Semenov","doi":"10.1134/S0006297924100158","DOIUrl":"https://doi.org/10.1134/S0006297924100158","url":null,"abstract":"<p><p>The kinetics of the primary electron donor P₇₀₀⁺ and the quinone acceptor A₁^- redox transitions were simultaneously studied for the first time in the time range of 200 μs-10 ms using high-frequency pulse Q-band EPR spectroscopy at cryogenic temperatures in various complexes of photosystem I (PSI) from the cyanobacterium <i>Synechocystis sp.</i> PCC 6803. In the A₁-core PSI complexes that lack 4Fe4S clusters, the kinetics of the A₁^- and P₇₀₀⁺ signals disappearance at 100 K were similar and had a characteristic time of τ ≈ 500 μs, caused by charge recombination in the P₇₀₀⁺A_1A^- ion-radical pair in the <i>A</i> branch of redox cofactors. The kinetics of the backward electron transfer from A_1B^- to P₇₀₀⁺ in the <i>B</i> branch of redox cofactors with τ &lt; 100 μs could not be resolved due to time limitations of the method. In the native PSI complexes with a full set of redox cofactors and in the F_X-core complexes, containing the 4Fe4S cluster F_X, the kinetics of the A₁^- signal was significantly faster than that of the P₇₀₀⁺ signal. The disappearance of the A₁^- signal had a characteristic time of 280-350 μs; it was suggested that, in addition to the backward electron transfer from A_1A^- to P₇₀₀⁺ with τ ≈ 500 μs, its kinetics also includes the forward electron transfer from A_1A^- to the 4Fe4S cluster F_X, which had slowed down to 150-200 μs. In the kinetics of P₇₀₀⁺ reduction, it was possible to distinguish components caused by the backward electron transfer from A₁^- (τ ≈ 500 μs) and from 4Fe4S clusters (τ = 1 ms for the F_X-core and τ &gt; 5 ms for native complexes). These results are in qualitative agreement with the data on the kinetics of P₇₀₀⁺ reduction obtained previously using pulse absorption spectrometry at cryogenic temperatures.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1851-1862"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Expression and Pathway Activation Biomarkers of Breast Cancer Sensitivity to Taxanes.","authors":"Daniil Luppov, Maxim Sorokin, Marianna Zolotovskaya, Marina Sekacheva, Maria Suntsova, Galina Zakharova, Anton Buzdin","doi":"10.1134/S0006297924100110","DOIUrl":"https://doi.org/10.1134/S0006297924100110","url":null,"abstract":"<p><p>Taxanes are one of the most widely used classes of breast cancer (BC) therapeutics. Despite the long history of clinical usage, the molecular mechanisms of their action and cancer resistance are still not fully understood. Here we aimed to identify gene expression and molecular pathway activation biomarkers of BC sensitivity to taxane drugs paclitaxel and docetaxel. We used to our knowledge the biggest collection of clinically annotated publicly available literature BC gene expression data (12 datasets, <i>n</i> = 1250) and the experimental clinical BC cohort (<i>n</i> = 12). Seven literature datasets were used for biomarker discovery (<i>n</i> = 914), and the remaining five literature plus one experimental datasets (<i>n</i> = 336) - for the validation. We totally found 34 genes and 29 molecular pathways which could strongly discriminate good and poor responders to taxane treatments. The biomarker genes and pathways were associated with molecular processes related to formation of mitotic spindle and centromeres, and with the spindle assembly mitotic checkpoint. Furthermore, we created gene expression and pathway activation signatures predicting BC response to taxanes. These signatures were tested on the validation BC cohort and demonstrated strong biomarker potential reflected by mean AUC values of 0.76 and 0.77, respectively, which outperforms previously reported analogs. Taken together, these findings can deepen our understanding of mechanism of action of taxanes and potentially improve personalization of treatment in BC.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1803-1822"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astaxanthin Reduces H₂O₂- and Doxorubicin-Induced Cardiotoxicity in H9c2 Cardiomyocyte Cells.","authors":"Roman R Krestinin, Margarita I Kobyakova, Yuliya L Baburina, Linda D Sotnikova, Olga V Krestinina","doi":"10.1134/S0006297924100122","DOIUrl":"https://doi.org/10.1134/S0006297924100122","url":null,"abstract":"<p><p>Cardiovascular diseases are among the most challenging problems in clinical practice. Astaxanthin (AST) is a keto-carotenoid (xanthophyll) mainly of marine origin, which is able to penetrate the cell membrane, localize in mitochondria, and prevent mitochondrial dysfunction. In this study effect of astaxanthin on the death of H9c2 cardiomyocytes caused by the cytotoxic effect of hydrogen peroxide (H₂O₂) and doxorubicin (DOX) was examined. Using methods of spectrophotometry, spectrofluorimetry, and Western blotting analysis, it was shown that treatment of the cells with AST contributed to the increase in the number of H9c2 cells resistant to H₂O₂ and doxorubicin, while maintaining the value of their mitochondrial transmembrane potential, reducing intracellular production of reactive oxygen species, and increasing intracellular content of the mitophagy markers PINK1, Parkin, and prohibitin 2. The obtained results suggest that the use of AST could be a highly effective way to prevent and treat cardiovascular diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1823-1833"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Expression of the <i>GRIPAP1</i>, <i>DLG4</i>, <i>KIF1B</i>, <i>NGFRAP1</i>, and <i>NRF1</i> Genes in Peripheral Blood of the Patients with Parkinson's Disease in the Early Clinical Stages.","authors":"Maria V Lukashevich, Margarita M Rudenok, Ekaterina I Semenova, Suzanna A Partevian, Alexey V Karabanov, Elena Yu Fedotova, Sergey N Illarioshkin, Petr A Slominsky, Maria I Shadrina, Anelya Kh Alieva","doi":"10.1134/S0006297924100092","DOIUrl":"https://doi.org/10.1134/S0006297924100092","url":null,"abstract":"<p><p>Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. An important feature of the disease is its long latent period, which necessitates search for prognostic biomarkers. One method of identifying biomarkers of PD is to study changes in gene expression in peripheral blood of the patients in early stages of the disease and have not been treated. In this study, we analyzed relative mRNA levels of the genes <i>GRIPAP1</i>, <i>DLG4</i>, <i>KIF1B</i>, <i>NGFRAP1</i>, and <i>NRF1</i>, which are associated with neurotransmitter transport, apoptosis, and mitochondrial dysfunction, in the peripheral blood of PD patients using reverse transcription and real-time PCR with TaqMan probes. The results of this study suggest that the <i>GRIPAP1</i> and <i>DLG4</i> genes could be considered as potential biomarkers for the early clinical stages of Parkinson's disease. The data obtained may indicate that <i>NGFRAP1</i> is involved in pathogenesis of both PD and other neurodegenerative diseases. Furthermore, in the early clinical stages of the disease we studied, the <i>KIF1B</i> and <i>NRF1</i> genes were found not to be involved in PD pathogenesis at the expression level.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1779-1788"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myogenic Classical Endocannabinoids, Their Targets and Activity.","authors":"Olga P Balezina, Ekaterina O Tarasova, Polina O Bogacheva","doi":"10.1134/S0006297924100080","DOIUrl":"https://doi.org/10.1134/S0006297924100080","url":null,"abstract":"<p><p>This review focuses on the recently discovered specific action of two classical endocannabinoids (ECs), 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (AEA), in the case of their synthesis and degradation in skeletal muscles; in other words, this review is dedicated to properties and action of the myoendocannabinoid (myoEC) pool. Influence of this pool is considered at three different levels: at the level of skeletal muscles, motor synapses, and also at the level of the whole organism, including central nervous system. Special attention is paid to the still significantly underestimated and intriguing ability of ECs to have positive effect on energy exchange and contractile activity of muscle fibers, as well as on transmitter secretion in motor synapses. Role of muscle contractions in regulation of activity balance between the enzymes catalyzing synthesis and degradation of myoECs and, therefore, in the release of myoECs and exertion of their specific effects is thoroughly considered. Increasingly popular hypotheses about the prominent role of myoECs (AEA and/or 2-AG) in the rise of the overall level of ECs in the blood during muscle exercise and the development of \"runner's high\" and about the role of myoECs in the correction of a number of psychophysiological conditions (pain syndrome, stress, etc.) are discussed here. Thus, this review presents information about the myoEC pool from a totally new viewpoint, underlining its possible independent and non-trivial regulatory role in the body, in contrast to the traditional and well-known activity of neurogenic ECs.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1759-1778"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial Cellulose-Chitosan Composite for Prolonged-Action L-Asparaginase in Treatment of Melanoma Cells.","authors":"Anastasia N Shishparenok, Egor R Petryaev, Svetlana A Koroleva, Natalya V Dobryakova, Igor D Zlotnikov, Elena N Komedchikova, Olga A Kolesnikova, Elena V Kudryashova, Dmitry D Zhdanov","doi":"10.1134/S0006297924100067","DOIUrl":"https://doi.org/10.1134/S0006297924100067","url":null,"abstract":"<p><p>A significant challenge associated with the therapeutic use of L-ASP for treatment of tumors is its rapid clearance from plasma. Effectiveness of L-ASP is limited by the dose-dependent toxicity. Therefore, new approaches are being developed for L-ASP to improve its therapeutic properties. One of the approaches to improve properties of the enzymes, including L-ASP, is immobilization on various types of biocompatible polymers. Immobilization of enzymes on a carrier could improve stability of the enzyme and change duration of its enzymatic activity. Bacterial cellulose (BC) is a promising carrier for various drugs due to its biocompatibility, non-toxicity, high porosity, and high drug loading capacity. Therefore, this material has high potential for application in biomedicine. Native BC is known to have a number of disadvantages related to structural stability, which has led to consideration of the modified BC as a potential carrier for immobilization of various proteins, including L-ASP. In our study, a BC-chitosan composite in which chitosan is cross-linked with glutaraldehyde was proposed for immobilization of L-ASP. Physicochemical characteristics of the BC-chitosan films were found to be superior to those of native BC films, resulting in increase in the release time of L-ASP <i>in vitro</i> from 8 to 24 h. These films exhibited prolonged toxicity (up to 10 h) against the melanoma cell line. The suggested strategy for A-ASP immobilization on the BC-chitosan films could be potentially used for developing therapeutics for treatment of surface types of cancers including melanomas.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1727-1743"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrafast Proteomics","authors":"Ivan I. Fedorov,&nbsp;Sergey A. Protasov,&nbsp;Irina A. Tarasova,&nbsp;Mikhail V. Gorshkov","doi":"10.1134/S0006297924080017","DOIUrl":"10.1134/S0006297924080017","url":null,"abstract":"<p>Current stage of proteomic research in the field of biology, medicine, development of new drugs, population screening, or personalized approaches to therapy dictates the need to analyze large sets of samples within the reasonable experimental time. Until recently, mass spectrometry measurements in proteomics were characterized as unique in identifying and quantifying cellular protein composition, but low throughput, requiring many hours to analyze a single sample. This was in conflict with the dynamics of changes in biological systems at the whole cellular proteome level upon the influence of external and internal factors. Thus, low speed of the whole proteome analysis has become the main factor limiting developments in functional proteomics, where it is necessary to annotate intracellular processes not only in a wide range of conditions, but also over a long period of time. Enormous level of heterogeneity of tissue cells or tumors, even of the same type, dictates the need to analyze biological systems at the level of individual cells. These studies involve obtaining molecular characteristics for tens, if not hundreds of thousands of individual cells, including their whole proteome profiles. Development of mass spectrometry technologies providing high resolution and mass measurement accuracy, predictive chromatography, new methods for peptide separation by ion mobility and processing of proteomic data based on artificial intelligence algorithms have opened a way for significant, if not radical, increase in the throughput of whole proteome analysis and led to implementation of the novel concept of ultrafast proteomics. Work done just in the last few years has demonstrated the proteome-wide analysis throughput of several hundred samples per day at a depth of several thousand proteins, levels unimaginable three or four years ago. The review examines background of these developments, as well as modern methods and approaches that implement ultrafast analysis of the entire proteome.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 8","pages":"1349 - 1361"},"PeriodicalIF":2.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297924080017.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMDA Receptors and Indices of Energy Metabolism in Erythrocytes: Missing Link to the Assessment of Efficiency of Oxygen Transport in Hepatic Encephalopathy","authors":"Gubidat A. Alilova,&nbsp;Lyudmila A. Tikhonova,&nbsp;Elena A. Kosenko","doi":"10.1134/S000629792408008X","DOIUrl":"10.1134/S000629792408008X","url":null,"abstract":"<p>Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that develops in patients with severe liver dysfunction and/or portocaval shunting. Despite more than a century of research into the relationship between liver damage and development of encephalopathy, pathogenetic mechanisms of hepatic encephalopathy have not yet been fully elucidated. It is generally recognized, however, that the main trigger of neurologic complications in hepatic encephalopathy is the neurotoxin ammonia/ammonium, concentration of which in the blood increases to toxic levels (hyperammonemia), when detoxification function of the liver is impaired. Freely penetrating into brain cells and affecting NMDA-receptor-mediated signaling, ammonia triggers a pathological cascade leading to the sharp inhibition of aerobic glucose metabolism, oxidative stress, brain hypoperfusion, nerve cell damage, and formation of neurological deficits. Brain hypoperfusion, in turn, could be due to the impaired oxygen transport function of erythrocytes, because of the disturbed energy metabolism that occurs in the membranes and inside erythrocytes and controls affinity of hemoglobin for oxygen, which determines the degree of oxygenation of blood and tissues. In our recent study, this causal relationship was confirmed and novel ammonium-induced pro-oxidant effect mediated by excessive activation of NMDA receptors leading to impaired oxygen transport function of erythrocytes was revealed. For a more complete evaluation of “erythrocytic” factors that diminish brain oxygenation and lead to encephalopathy, in this study, activity of the enzymes and concentration of metabolites of glycolysis and Rapoport–Lubering shunt, as well as morphological characteristics of erythrocytes from the rats with acute hyperammoniemia were determined. To elucidate the role of NMDA receptors in the above processes, MK-801, a non-competitive receptor antagonist, was used. Based on the obtained results it can be concluded that it is necessary to consider ammonium-induced morphofunctional disorders of erythrocytes and hemoglobinemia which can occur as a result of alterations in highly integrated networks of metabolic pathways may act as an additional systemic “erythrocytic” pathogenetic factor to prevent the onset and progression of cerebral hypoperfusion in hepatic encephalopathy accompanied by hyperammonemia.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 8","pages":"1490 - 1508"},"PeriodicalIF":2.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}