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

{"title":"Theoretical Models of Mechanisms of Membrane Activity of Linear Amphipathic Peptides","authors":"O. V. Kondrashov,&nbsp;S. A. Akimov","doi":"10.1134/S1990747826700194","DOIUrl":"10.1134/S1990747826700194","url":null,"abstract":"<p>Linear amphipathic peptides are components of some natural venoms exhibiting pronounced cytolytic activity. They are characterized by a low selectivity and a receptor-independent mechanism of action. Their common structural property is a spatial separation of hydrophobic and polar (charged) amino acid residues within a single molecule, as well as a relatively large positive electrical charge. Cytolytic peptides of venoms exhibit antimicrobial properties and are considered prototypes for potential antibiotics. Classical antimicrobial peptides have the same structural properties as the cytolytic peptides of natural venoms. Amphipathic peptides form pores in lipid membranes by two possible mechanisms: local and nonlocal. The local mechanism involves membrane destabilization immediately adjacent to the peptide molecule, partially embedded in the lipid monolayer. The nonlocal mechanism works only on closed membranes with one-sided addition of amphipathic peptides. In this case, the incorporation of peptides into the contact membrane monolayer induces lateral pressure in it and lateral tension in the opposite monolayer. This asymmetry in lateral tension/pressure facilitates the formation of large metastable lipid pores. In this study, we performed a theoretical analysis of the nonlocal mechanism of pore formation. Using the theory of lipid membrane elasticity, we calculated the dependences of pore energy on radius for various values of lateral tension and pressure in membrane monolayers and determined the dependences of the energy barriers to the formation and closure of a metastable pore, as well as of its radius, on lateral tension/pressure. A mechanism for the local formation of through defects in the membrane by single molecules of amphipathic peptides is proposed. Lipids and amphipathic peptides can pass through the defect walls to the opposite membrane monolayer. The structural characteristics of the peptides responsible for the efficient formation of defects are determined.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"326 - 342"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719064","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":"Cytolytic Peptides from Oxyopes takobius Spider Venom Inhibit Chlamydial Growth","authors":"N. F. Polina,&nbsp;E. S. Kostryukova,&nbsp;A. A. Vassilevski,&nbsp;E. V. Grishin,&nbsp;V. N. Lazarev","doi":"10.1134/S1990747826700200","DOIUrl":"10.1134/S1990747826700200","url":null,"abstract":"<p>Cytolytic peptides are a large, heterogeneous group of proteinaceous compounds capable of disrupting the integrity of biological membranes and causing cell lysis. Arthropod venom is a rich source of cytolytic peptides. Melittin from honeybee venom, as well as several peptides from the venom of the spider <i>Lachesana tarabaevi</i>, have previously been demonstrated to inhibit the growth of the intracellular parasitic bacterium <i>Chlamydia trachomatis</i>. In this study, using the Tet-On system for regulated gene expression in HEK293 cells, it was demonstrated that oxyopinins—cytolytic peptides derived from the venom of the spider <i>Oxyopes takobius</i>—exhibit similar anti-chlamydial activity. Oxyopinins have diverse amino acid sequences and are not homologous to previously studied peptides. This work significantly expands the range of known compounds with anti-chlamydial activity.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"343 - 348"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719108","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":"Editorial Foreword","authors":"S. S. Kolesnikov","doi":"10.1134/S1990747826030013","DOIUrl":"10.1134/S1990747826030013","url":null,"abstract":"","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"251 - 251"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719113","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":"Eugene V. Grishin, a Founder of Modern Toxinology","authors":"A. A. Vassilevski","doi":"10.1134/S1990747826700133","DOIUrl":"10.1134/S1990747826700133","url":null,"abstract":"<p>On April 16, 2026, Eugene V. Grishin would have turned 80. Eugene has been gone for ten years now, but his contribution to the science of membrane receptors is so significant that the influence of his work and ideas on our research is still felt today. In this article, I will discuss some memorable events related to Grishin in the scientific community.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"252 - 255"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719140","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":"Physiological Regulation and Pharmacology of Two-Pore Calcium Channels of the Endolysosomal System","authors":"P. V. Avdonin,&nbsp;S. K. Trufanov,&nbsp;N. V. Goncharov,&nbsp;E. S. Kuzmina,&nbsp;E. Yu. Rybakova,&nbsp;P. P. Avdonin","doi":"10.1134/S1990747826700145","DOIUrl":"10.1134/S1990747826700145","url":null,"abstract":"<p>Two-pore calcium channels (TPCs) are localized in the membranes of endosomes and lysosomes and play a crucial role in the regulation of vesicular transport, autophagy, protein, nucleic acid, and lipid catabolism, recycling of plasma membrane receptors, and other processes occurring in the endolysosomal system. Humans express two types of channels, TPC1 and TPC2. Dysfunction of these channels is the cause of severe pathologies, including cancer and neurodegenerative diseases. Understanding the mechanisms of TPC channel regulation and identifying pharmacological pathways to influence their activity are essential for developing new approaches to the prevention and treatment of these diseases. This review characterizes the properties of two-pore channels and describes their regulation by phosphatidylinositol-3,5-bisphosphate and NAADP (nicotinic acid adenine dinucleotide phosphate), changes in channel activity during cell starvation, as well as the effects on TPC channels exerted by sphingosine, protein kinases P38 and JNK, and regulatory proteins mTor, Rab7a, and Tmem63a. Information on the pharmacology of TPC channels is provided. Groups of NAADP receptor site antagonists and compounds acting directly on the channel protein are highlighted. Part of the review is devoted to the description of plant-derived channel regulators and their potential use as anticancer drugs.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"256 - 274"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719142","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 Effect of Media, Conditioned by Serratia proteamaculans and Enriched with ShlA Toxin, on the Permeability of Lipid Bilayers, Mimicking the Membranes of Epithelial Cells HeLa and Caco-2","authors":"I. I. Zaripov,&nbsp;P. D. Zlodeeva,&nbsp;S. S. Efimova,&nbsp;O. A. Tsaplina,&nbsp;O. S. Ostroumova","doi":"10.1134/S1990747826700182","DOIUrl":"10.1134/S1990747826700182","url":null,"abstract":"<p>In this work we investigated the pore-forming activity of ShlA toxin from <i>Serratia proteamaculans</i> in lipid bilayers modelling the membranes of epithelial cells HeLa and Caco-2 and assessed the role of CaCl₂ in its modification. It was found that the addition of conditioned <i>S. proteamaculans</i> media enriched with ShlA toxin to planar lipid bilayers formed from 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphocholine (POPC)/sphingomyelin (SM)/cholesterol (CHOL) (33/33/33 mol %) or POPC/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoethanolamine (POPE)/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phospho-<i>L</i>-serine (POPS)/SM/CHOL (30/30/5/10/25 mol %) leads to the formation of ion-permeable pores. The mean amplitude of currents flowing through single ShlA channels formed in POPC/POPE/POPS/SM/CHOL membranes was smaller than in bilayers of POPC/SM/CHOL. The current-voltage characteristics of channels formed by ShlA from <i>S. proteamaculans</i> in bilayers of both compositions were nonlinear. The application of media conditioned by <i>S. proteamaculans</i> did not increase the permeability of POPC/SM/CHOL and POPC/POPE/POPS/SM/CHOL vesicles for the fluorescent marker calcein. The addition of 10 mM CaCl₂ potentiated the pore-forming activity of ShlA from <i>S. proteamaculans</i> in planar lipid bilayers, which manifested itself in the emergence of substates with higher conductivity. The joint addition of ShlA-enriched media conditioned by <i>S. proteamaculans</i> and 10 mM CaCl₂ increased the permeability of POPC/POPE/POPS/SM/CHOL vesicles for calcein, but not of liposomes formed from POPC/SM/CHOL. In addition, it was demonstrated that in the presence of 10 mM CaCl₂, there was a significant increase in the invasion of <i>S. proteamaculans</i> into Caco-2 cells, which could be mediated by an increase in the membrane activity of the ShlA toxin. The results obtained expand our understanding of the composition of the media conditioned by <i>S. proteamaculans</i> and the mechanisms of molecular action of the ShlA toxin on epithelial cell membranes.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"314 - 325"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719141","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":"Neurotoxins As Tools for Studying Neuromuscular Transmission in Cholinergic Synapses","authors":"E. A. Bukharaeva,&nbsp;A. M. Petrov","doi":"10.1134/S1990747826700157","DOIUrl":"10.1134/S1990747826700157","url":null,"abstract":"<p>Cholinergic neuromuscular synapses in skeletal and respiratory muscles play a crucial role in respiration and movement, transmitting excitation from the motor neuron to the muscle fibers. Key players in this process include voltage-gated ion channels, the machinery for releasing neurotransmitter acetylcholine from nerve terminals, and receptor–channel complexes on the muscle fiber membrane. Neurotoxins specific to various molecular structures involved in synaptic function are widely used to investigate the molecular mechanisms underlying the processes that ensure the plasticity and high reliability of the synaptic machinery. This review examines presynaptic and postsynaptic neurotoxins that act on ion channels, neurosecretory processes, and postsynaptic receptors and are used to study neuromuscular transmission.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"275 - 289"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719143","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":"Modulation of Noradrenaline-Induced cAMP Production in HEK-293 Cells by Insulin","authors":"E. A. Dymova,&nbsp;O. A. Rogachevskaja,&nbsp;P. D. Kotova,&nbsp;N. P. Kovalenko,&nbsp;S. S. Kolesnikov","doi":"10.1134/S1990747826700170","DOIUrl":"10.1134/S1990747826700170","url":null,"abstract":"<p>The first messengers regulate cellular functions by involving surface receptors coupled to diverse intracellular signaling pathways. Those do not function completely independently, and an increasing body of evidence argues for the existence of crosstalk between signaling systems and their coordination. Here we analyzed a potential contribution of the PI3K–Akt cascade to the regulation of cAMP signaling initiated by noradrenaline (NA) in HEK-293 cells that expressed Pink Flamindo, a genetically encoded cAMP sensor, at a constant and high level. This feature makes this cell line a sufficiently effective cellular model for the analysis of mechanisms involved in the generation of intracellular cAMP signals. As was shown, the stimulation of β‑adrenoreceptors (β-AR) by NA led to a rise in cAMP in HEK-293 cells. Being applied shortly for 100–150 s, NA initiated cAMP signals, the magnitude of which gradually increased with an agonist concentration, exhibiting the EC₅₀ of about 1 µM. In the presence of 150 nM insulin, the magnitude of cAMP responses to 1 µM NA decreased by 31% on average compared to control. The inhibitors of PI3K and Akt, wortmannin (10 µM) and GSK690693 (5 µM), respectively, which as such did not affect cAMP responses of cells, canceled inhibitory effects of insulin on cAMP signaling triggered by NA. This indicated that insulin diminished NA-induced cAMP signals by involving insulin receptors coupled to the PI3K–Akt pathway, which, in turn, modulated efficacy of NA transduction mediated by the signaling cascade β-AR–Gs-protein–adenylate cyclase/phosphodiesterase (PDE). Reportedly, the phosphorylation of PDE3 by Akt stimulated this cAMP-specific PDE isoform, the phenomenon that could account for the decrease of cAMP signals observed in the presence of insulin. Supporting this idea was that selective PDE3 inhibitor Trequinsin (4 µM) per se gave rise to intracellular cAMP, indicating that the activity of PDE3 in non-stimulated cells was sufficiently high. At the same time, insulin decreased cAMP responses to Trequinsin by 36% compared to control. The overall data obtained here suggest that insulin can modulate cAMP responses of HEK-293 cells to NA largely due to coupling of the insulin receptor to the PI3K–Akt pathway that controlled activity of cAMP-hydrolyzing PDE3 in an insulin-dependent manner.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"306 - 313"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719145","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":"Modulation of the Fluoroacetate Effects on Calcium Balance and Mitochondrial Potential in Primary Culture of Rat Hippocampal Cells","authors":"E. A. Turovsky,&nbsp;M. V. Turovskaya,&nbsp;V. P. Zinchenko,&nbsp;N. V. Goncharov","doi":"10.1134/S1990747826700212","DOIUrl":"10.1134/S1990747826700212","url":null,"abstract":"<p>Fluoroacetate (FA) is a metabolic poison whose toxic effect is caused by the inhibition of mitochondrial aconitase, leading to the accumulation of citrate in cells and target organs, primarily in the brain, spinal cord, heart, and kidneys. Previously, during the development of a treatment regimen for acute FA poisoning, a positive effect of methylene blue (MB) on the survival of experimental animals was revealed. The mechanism of action of MB in acute FA intoxication has not been established; however, based on the physicochemical characteristics and effects of MB described in the literature, we hypothesized that MB, as an artificial electron acceptor, promotes citrate utilization via cytoplasmic aconitase and isocitrate dehydrogenase, which leads to a decrease in citrate levels and restoration of Ca²⁺ ion balance. The aim of this study is to identify the effects of FA on calcium balance and mitochondrial potential in astrocytes and hippocampal neurons of rats under in vitro conditions, as well as the nature of the modulation of these effects by methylene blue, the transmembrane electron transport inhibitor 4-hydroxycoumarin (4HC), the Ca²⁺ chelator BAPTA, and the ryanodine receptor inhibitor dantrolene. It was found that FA causes death of astrocytes, but not neurons, in primary hippocampal cultures, which is associated with an increase in intracellular calcium ion levels ([Ca²⁺]_i). Citrate has no toxic effect on astrocytes but potentiates the drop in mitochondrial membrane potential in response to FA. 4-Hydroxycoumarin suppresses the calcium response in neurons and has virtually no effect on astrocytes. However, 4HC suppresses changes in the mitochondrial potential of astrocytes. In response to the addition of FA in the presence of citrate, dantrolene prevents an increase in [Ca²⁺]_i, especially in neurons. At the same time, MB neutralizes the effect of FA, preventing a decrease in the rate of mitochondrial potential change in both neurons and astrocytes. Thus, the effects of MB on astrocytes may be associated with the inhibition of transmembrane electron transport, a reduction in the level of reactive oxygen species, and the modulation of ryanodine receptor sensitivity. The observed effects support our hypothesis regarding the molecular mechanism of action of MB in astrocytes; however, further experiments are needed to obtain direct evidence.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"349 - 360"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719063","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":"Potassium Channels Kv7 (KCNQ) and GIRK As Universal Regulators of Neuromuscular Activity","authors":"I. V. Kovyazina,&nbsp;A. N. Tsentsevitsky,&nbsp;A. M. Petrov","doi":"10.1134/S1990747826700169","DOIUrl":"10.1134/S1990747826700169","url":null,"abstract":"<p>Potassium channels are the most diverse superfamily of ion channels, controlling many cellular functions. In this review, we focused on describing the properties of potassium channels of the Kv7 (KCNQ) and GIRK (KCNJ) families. We pay particular attention to the role of these channels in regulating neuromuscular transmission and skeletal muscle activity. Although Kv7 and GIRK channels belong to different classes of potassium channels, they perform similar functions by controlling cellular excitability. In skeletal muscles and motor nerve terminals, Kv7 and GIRK channel subtypes, located at the intersection of many signaling pathways, are involved in regulating the muscle fiber contractility and the intensity of spontaneous and evoked release of the neurotransmitter acetylcholine. Kv7 and GIRK channels are targets for a number of endogenous modulators and toxins, and their dysfunction is associated with the pathogenesis of a wide range of disorders. A detailed study of the properties and functions of Kv7 and GIRK potassium channels will provide a deeper understanding of the therapeutic potential of using their antagonists and agonists for the treatment of various neurological, including neuromuscular, diseases.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 3","pages":"290 - 305"},"PeriodicalIF":0.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719144","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}