Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology最新文献

{"title":"In Silico Evaluation of the Effect of Geometrical Configuration and Charge of Opioid Antagonists on Their Binding to Receptors","authors":"D. V. Krivorotov,&nbsp;D. A. Belinskaia,&nbsp;A. S. Smirnov,&nbsp;V. V. Suslonov,&nbsp;N. V. Goncharov,&nbsp;V. A. Kuznetsov","doi":"10.1134/S1990747825700254","DOIUrl":"10.1134/S1990747825700254","url":null,"abstract":"<p>The effect of the geometric configuration and charge of membrane opioid receptor (OR) agonists and antagonists on binding to μ, δ, and κ opioid receptors has been studied by molecular docking. For the docking procedure, three-dimensional structures of pharmaceutical preparations obtained by X-ray diffraction analysis (XRD) and available in the Cambridge Crystal Structures Database (CCDC), as well as their three-dimensional models constructed in a molecular editor, were used. The three-dimensional crystal structure of nalmefene, which is absent in the CCDC database, was first obtained in the presented study by XRD. Protonated and deprotonated forms of ligands were considered. The results of the study using morphine, codeine, naloxone, naltrexone, and nalmefene as examples showed that the method of obtaining three-dimensional geometric structures of opioid receptor ligands practically did not affect the calculated free energy of binding ΔG, which indicates the possibility of using ligand models constructed <i>in silico</i> in computational experiments. The protonation state of the ligand molecule, on the contrary, had a significant effect on free energy of binding to OR, which might affect the properties of this group of drugs with pH changes in the body. When considering the binding features of opioid enantiomers to the ligand-binding site of μ-opioid receptors, using morphine as an example, it was shown that (–)-morphine and (+)-morphine share a common site for the cationic group, and not for phenolic hydroxyl, as previously assumed. At the same time, studies have shown that molecular docking only partially made it possible to describe the pharmacological effect of analgesics and their antagonists. For some substances, such as codeine and synthetic (+)-morphine, the experiment <i>in silico</i> overestimated the effectiveness of the drug’s interaction with OR, and this requires continued improvement of the corresponding calculation methods and models.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"303 - 317"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of KV and BK Channels in the Effects of Sodium Butyrate on Colon Motility in a Mouse Model of Irritable Bowel Syndrome","authors":"I. F. Shaidullov,&nbsp;D. Bouchareb,&nbsp;D. M. Sorokina,&nbsp;G. F. Sitdikova","doi":"10.1134/S1990747825700308","DOIUrl":"10.1134/S1990747825700308","url":null,"abstract":"<p>Irritable bowel syndrome (IBS) is a multifactorial disorder, with a high socioeconomic impact, characterized by chronic abdominal pain, bloating, and alterations in bowel habits. The aim of our study was to study the role of voltage gated and large conductance calcium-activated potassium channels in the effect of sodium butyrate on spontaneous and induced by agonists of cholinoreceptors contractions of proximal colon in a mouse model of IBS. IBS was induced by intracolonic infusion of acetic acid in the early postnatal period. The contractile activity of proximal colonic segments was then studied in isometric conditions. The amplitude and frequency of colon contractions were higher in the IBS group. Sodium butyrate demonstrated an inhibitory effect on the amplitude of spontaneous and cholinoreceptor agonist-induced contractions of colon, with lower efficiency in the IBS group. Application of the inhibitors of voltage gated and large conductance calcium-activated potassium channels (BK channels) revealed that BK channels are involved in the inhibitory effects of sodium butyrate on spontaneous and evoked contractile activity in the control group. In the IBS group, BK inhibitor was not effective to prevent sodium butyrate effects on the amplitude of spontaneous contractions; however, it prevented the inhibitory effects of sodium butyrate on the amplitude of contractions induced by epibatidine. We conclude that the inhibitory effects of sodium butyrate on the amplitude of spontaneous and carbachol-/epibatidine-induced contractions are mediated by activation of BK channels of smooth muscle cells or cholinergic terminals. Activation of these channels results in membrane hyperpolarization and a reduction in acetylcholine release with further decreased contractile activity.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"348 - 355"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Line Tension of Pore Edge in Membrane on Solid Support","authors":"D. I. Kostina,&nbsp;M. V. Sumarokova,&nbsp;S. P. Dudik,&nbsp;P. V. Bashkirov,&nbsp;S. A. Akimov","doi":"10.1134/S1990747825700217","DOIUrl":"10.1134/S1990747825700217","url":null,"abstract":"<p>Controlled formation of through pores in bilayer lipid membranes is a key stage of various biotechnological techniques. Excess energy of the pore edge is characterized by line tension, the value of which determines the overall stability of the membrane with respect to pore formation. The practically important pore size is on the order of a few nanometers. It is impossible to study such pores by direct optical methods, but they can, in principle, be visualized by atomic force microscopy. This method uses a solid support on which the lipid bilayer is held due to the interaction of one of the monolayers with it. In this work, we theoretically investigated the effect of the presence of the support on the value of the line tension of the pore edge. It was assumed that the line tension is determined by the energy of elastic deformation of the membrane at the edge. Various regimes of membrane interaction with the support were considered: from a free-standing membrane (complete absence of interaction) to the case of infinitely strong adhesion of the membrane to the support. The calculation results show that the relative change in the line tension of the pore edge within such variation of the intensity of the interaction of the membrane with the support is less than 3.5%. Thus, the developed theoretical model predicts an extremely weak effect of the interaction with the support on the magnitude of the line tension–the main energy characteristic of the pore edge.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"259 - 267"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant Protein Biosensors of Cell Membrane Lipids","authors":"E. M. Koltsova,&nbsp;N. A. Kolchin,&nbsp;E. I. Nikolaeva,&nbsp;K. R. Butov","doi":"10.1134/S1990747825700205","DOIUrl":"10.1134/S1990747825700205","url":null,"abstract":"<p>Specific patterns of lipid distribution in cell membranes determine their structural and signaling roles and ensure the integrity and functionality of the plasma membrane and cell organelles. Recent advances in the development of recombinant lipid biosensors and imaging techniques allow direct observation of the distribution, movement, and dynamics of lipids within cells, significantly expanding the understanding of lipid functions and their involvement in cellular and subcellular processes. In this review, we summarize the data related to the development and application of recombinant protein sensors for various lipids in cell membranes.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"241 - 258"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Protective Role of Mangiferin and trans-Cinnamic Acid against Oxidative Stress in Wild Type and aak-2 Mutant Caenorhabditis elegans Strains","authors":"S. S. Salimon,&nbsp;S. V. Leonov,&nbsp;E. I. Marusich","doi":"10.1134/S1990747825700321","DOIUrl":"10.1134/S1990747825700321","url":null,"abstract":"<p>During cellular metabolism, reactive oxygen species and nitrogen species are produced which inherently results in oxidative damage of DNA and proteins. As a survival mechanism, these stressors modulate gene expression and various signalling pathways in <i>C.</i> <i>elegans</i>. The resistance to various forms of stress peaks in early adulthood and thereafter, decreases with age. In <i>C. elegans</i>, the gene <i>aak-2</i> enables the adenosine monophosphate (AMP)-activated protein kinase activity which is involved in stress responses, germ cell cycle arrest during dauer formation, and maintenance of longevity. In this study, we evaluated the effects of mangiferin (MF) and <i>trans</i>-cinnamic acid (TCA) at concentrations of 10, 50, 100, and 200 µM on the survival rate, lifespan, and motility of <i>C. elegans</i> treated with hydrogen peroxide<i>.</i> The nematodes (wild type N2-Bristol and <i>aak-2</i> mutant strains) were exposed to oxidative stress and then observed for the computation of percentage of survival (survival rate), motility, and maximum lifespan (ML). Treatment of wild-type <i>C. elegans</i> exposed to oxidative stress with TCA at concentrations of 50, 100, and 200 μM significantly (<i>p</i> &lt; 0.05) increased the survival rate and ML of nematodes compared to the control. Furthermore, MF at all doses studied significantly (<i>p</i> &lt; 0.05) increased the survival rate and extended the life span of H₂O₂-stressed wild-type nematodes fourfold. In the <i>aak-2</i> mutant strain, the survival rate and ML were only increased in the nematodes treated with 100 and 200 µM of TCA. There was also a dose-dependent increase in survival rate and ML of nematodes treated with MF. MF at the concentration of 200 µM prolonged the lifespan of nematodes by 5 days and restored motility function in 30% of the total nematode population.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"363 - 371"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wide-Angle X-Ray Scattering Comparative Analysis of Haloarchaeal Purple and Claret Membranes","authors":"E. A. Dronova,&nbsp;O. V. Semkin,&nbsp;A. Yu. Shishkin,&nbsp;D. D. Kuklina,&nbsp;A. O. Bogorodskiy,&nbsp;T. S. Kurkin,&nbsp;I. O. Bezruchko,&nbsp;L. M. Vasilenko,&nbsp;Yu. S. Semenov,&nbsp;S. V. Kalenov,&nbsp;A. I. Kuklin,&nbsp;Yu. L. Ryzhykau","doi":"10.1134/S199074782570028X","DOIUrl":"10.1134/S199074782570028X","url":null,"abstract":"<p>We present the results of the study of the structural distinctions between the purple membrane (PM) of <i>Halobacterium salinarum</i> and the claret membrane (CM) of <i>Haloquadratum walsbyi</i> using small-angle and wide-angle X-ray scattering. PM and CM are rhodopsin-rich membrane regions. They are crucial for light-driven energy processes in extreme halophilic archaea. While PM structure has been extensively characterized, the structure of CM remains less understood. According to our data, PM exhibits a well-defined hexagonal crystalline lattice with unit cell parameters of <i>a</i> = <i>b</i> ≈ 62 Å, which is consistent with published data. Conversely, CM showed unexpected diffraction patterns, best fitted by rhombohedral lattice with unit cell dimensions <i>a</i> = <i>b</i> = 27.9 Å; γ = 82.9°. But the presence of several unindexed peaks indicates the complexity of the CM sample. These structural differences are attributed to variations in native lipid and pigment compositions, specifically the presence of bacterioruberin in CM, as confirmed by UV-visible spectroscopy. Bacterioruberin, a hallmark of CM, contributes to its red-shifted absorption spectrum, indicative of its organized state within the membrane. However, denaturing 12% polyacrylamide gel electrophoresis (SDS-PAGE) and electron microscopy reveal potential contamination in CM samples, suggesting the need for improved purification protocols. The findings highlight significant structural disparities between PM and CM, with implications for understanding membrane organization. This research underscores the critical role of lipids and pigments in shaping the supramolecular architecture of archaeal membranes and provides a foundation for future studies into their functional adaptations.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"331 - 337"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of Angiotensin II Receptor Type 1 Production for Biophysical Studies","authors":"I. A. Kapranov,&nbsp;P. A. Khorn,&nbsp;D. E. Dashevskii,&nbsp;A. P. Luginina,&nbsp;I. S. Levashov,&nbsp;H. Zhang,&nbsp;A. V. Mishin,&nbsp;V. I. Borshchevskiy","doi":"10.1134/S1990747825700333","DOIUrl":"10.1134/S1990747825700333","url":null,"abstract":"<p>The class of G protein-coupled receptors (GPCRs) represents a ubiquitous family of membrane proteins that selectively interact with a variety of signaling molecules to modulate cellular biochemical and physiological processes. Consequently, the structural and functional investigation of GPCRs is of paramount importance for both fundamental and applied scientific research. However, challenges arise in their recombinant expression, as well as subsequent extraction and purification, due to their inherent thermal instability and low yield. This necessitates the optimization of expression conditions and protocols for solubilization and purification. In this study, we focused on optimizing the expression, solubilization, and purification processes for the angiotensin II type 1 receptor (AT1), which plays a critical role in the physiology of the cardiovascular system. Several critical factors affecting receptor expression levels, yield, and monomericity were identified, facilitating an enhancement in the quality of the produced protein.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"372 - 380"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Functional and Proliferative Activity of hTERT-NK and iCasp9-NK Cells","authors":"A. I. Palamarchuk,&nbsp;M. O. Ustiuzhanina,&nbsp;E. I. Kovalenko,&nbsp;M. A. Streltsova","doi":"10.1134/S1990747825700291","DOIUrl":"10.1134/S1990747825700291","url":null,"abstract":"<p>Cancer progression is often accompanied with the acquisition of functional anergy by natural killer (NK) cells and their aging. As a result, persistent herpesviruses, such as hCMV and EBV, reactivate. The catalytic subunit of telomerase encoded by <i>hTERT</i> gene may enhance functional and proliferative activity. We aimed to elucidate if NK cells modified for sustained hTERT expression acquire these beneficial characteristics. We examined the proliferative and functional activities of hTERT-NK cells and combined observations with RNA-seq results. Thus, hTERT-NK cells were characterized with an increase in the expression levels of cell cycle genes and better proliferative activity in the third month after isolation. Increased degranulation upon K562 target cell recognition simultaneously with a higher expression level of granzyme B was observed for hTERT-NK cells. An increased level of IFNγ was also noted in hTERT-NK cells. These results reveal that hTERT-NK cells obtain additional advantages due to the stable hTERT expression. hTERT-NK cells are likely to perform high levels of functional activity over long time periods that are commonly needed during cancer treatment to perform immune surveillance and minimize relapse rates.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"338 - 347"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thermodynamics of a Lipid Membrane with Curvature","authors":"A. A. Drozdova","doi":"10.1134/S1990747825700266","DOIUrl":"10.1134/S1990747825700266","url":null,"abstract":"<p>The work considers the transverse bending of the surface of a bilayer lipid membrane and the lateral pressure profile in the neutral part of the membrane within the framework of the model of lipid molecules as flexible elastic chains. When the shape of the membrane changes, the lateral pressure profile may also change. Using the renorm group, the addition to the lateral pressure profile during transverse bending of the membrane was calculated. The tilt moduli for several lipid species were calculated. Torsional modulus and Gaussian modulus calculations were performed for model membranes consisting of polymer rods. The results of the calculations are compared with available experimental and molecular dynamics data.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"318 - 323"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MKT-077 Suppresses the Functional Activity of Isolated Mouse Skeletal Muscle Mitochondria","authors":"A. D. Igoshkina,&nbsp;N. V. Mikina,&nbsp;A. V. Chulkov,&nbsp;E. I. Khoroshavina,&nbsp;M. V. Dubinin","doi":"10.1134/S1990747825700242","DOIUrl":"10.1134/S1990747825700242","url":null,"abstract":"<p>This study demonstrates the effect of the rhodocyanine derivative MKT-077 on the function of isolated mitochondria from mouse skeletal muscle. MKT-077 was shown to dose-dependently inhibit mitochondrial respiration fueled by glutamate/malate (complex I substrates) or succinate (complex II substrate). This effect of MKT-077 was accompanied by a decrease in the membrane potential of organelles and was associated with both inhibition of the activity of complexes I and II of the mitochondrial respiratory chain and an increase in the proton permeability of the inner mitochondrial membrane. Molecular docking revealed sites in mitochondrial respiratory chain complex I that have an affinity for MKT-077 comparable to that of the specific inhibitor rotenone. At a concentration of 5 μM, MKT-077 caused a significant increase in hydrogen peroxide production by skeletal muscle mitochondria. However, 1 μM MKT-077 reduced the pro-oxidant effect of antimycin A. In addition, MKT-077 dose-dependently reduced the ability of mitochondria to uptake and retain calcium ions in the matrix. The article discusses the mechanisms of possible action of MKT-077 on the functioning of skeletal muscle mitochondria and their contribution to the side effects observed during the therapy of pathological conditions in vivo using this rhodocyanine derivative.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"19 3","pages":"293 - 302"},"PeriodicalIF":1.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144868848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}