Biochemistry (Moscow)最新文献

{"title":"Plant Innate Immunity: Crosstalk of Signaling Pathways","authors":"Boris I. Skulachev,&nbsp;Anastasia K. Atabekova,&nbsp;Alexander A. Lezzhov,&nbsp;Andrey G. Solovyev","doi":"10.1134/S0006297925604289","DOIUrl":"10.1134/S0006297925604289","url":null,"abstract":"<p>The innate immunity of plants is a dynamic, multilevel system traditionally divided into pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). Despite being activated by different types of receptors localized in different cell compartments, PTI and ETI are currently considered interdependent components of a single defense system. This view suggests that, due to various positive interactions between these two pathways, the innate immunity of plants is more than the sum of PTI and ETI. Available data indicate that PTI and ETI enhance each other synergistically, increasing the concentration of signaling molecules, such as components of kinase cascades, reactive oxygen species, calcium ions, and phytohormones. This leads to the activation of defense genes, providing a local response to pathogens and the development of systemic plant resistance.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 4","pages":"543 - 560"},"PeriodicalIF":2.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757194","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":"Lymphotoxin Beta Receptor, but Not Its Lymphotoxin Alpha-Containing Ligands, Is Essential for the Development of Experimental Dermatitis","authors":"Ekaterina A. Gorshkova,&nbsp;Marina S. Drutskaya,&nbsp;Sergei A. Nedospasov,&nbsp;Ekaterina O. Gubernatorova","doi":"10.1134/S0006297926600080","DOIUrl":"10.1134/S0006297926600080","url":null,"abstract":"<p>Allergic contact dermatitis (ACD) is a chronic inflammatory skin disorder the development of which is driven by allergen sensitization in peripheral lymphoid organs and local cutaneous inflammation. Lymphotoxin (LT) and its receptor LTβR are critical for lymphoid organogenesis and immune regulation in barrier tissues, but their role in ACD pathogenesis remains incompletely defined. This study aimed to delineate differential contribution of the LTβR-dependent signaling in oxazolone-induced dermatitis. We examined Lta knockout (Lta KO) mice, which lack both soluble LTα3 and membrane-bound isoforms LTα1β2/LTα2β1, and the Ltbr knockout (Ltbr KO) mice, both of which lack lymph nodes. ACD was induced by repeated oxazolone application to ear skin, with assessment of clinical severity, inflammation-associated gene expression, serum IgE levels, and immune cell composition in blood and spleen. Contrary to previous reports, the Lta KO mice developed dermatitis comparable to the wild-type (WT) mice, with elevated IgE production. In contrast, the Ltbr KO mice were substantially protected from the disease, exhibiting attenuated clinical inflammation, reduced ear swelling, and decreased <i>Tslp</i> expression in the lesional skin at the background of a lower proportion of circulating CD4⁺ T cells. These findings indicate that LTβR-dependent signaling is pathogenic in allergic skin inflammation, while LTα-mediated pathways are dispensable, suggesting a potential role for the other LTβR ligand, LIGHT, in ACD pathogenesis. Notably, ACD developed even in the absence of lymph nodes, highlighting the importance of local, skin-resident LTβR-dependent mechanisms in the disease development.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 4","pages":"601 - 611"},"PeriodicalIF":2.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757205","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":"Parameters of Delayed Neuroinflammation Following Focal Ischemic Stroke in the Mouse Cerebral Cortex Depend on Lesion Size at the Beginning of the Subacute Stage","authors":"Vyacheslav I. Alekseev,&nbsp;Evgenia N. Kislukhina,&nbsp;Natalia V. Lizunova,&nbsp;Alexander M. Surin,&nbsp;Tatiana V. Lipina,&nbsp;Kirill V. Savostyanov,&nbsp;Zanda V. Bakaeva","doi":"10.1134/S0006297925604009","DOIUrl":"10.1134/S0006297925604009","url":null,"abstract":"<p>Dynamics of glial activity changes in the subacute and chronic stages of ischemic stroke after small focal injuries remains poorly understood due to complexity of the long-term animal monitoring and data interpretation. The aim of this study was to assess relationship between the delayed morphological changes in nervous tissue after experimental stroke and lesion parameters determined <i>in vivo</i> at various time points. For this purpose, photothrombotic ischemia of the cerebral cortex was induced in the C57BL/6J-Tg(Thy1-GCaMP6f)GP5.17Dkim/J mice, which express fluorescent calcium sensor protein GCaMP6f in cortical neurons. Lesion (ischemic core) size was determined using wide-field optical imaging (WFOI) through a cranial window via the GCaMP6f fluorescence at 3 min, 1 day, and 7 days post-photothrombosis. On day 19, brain sections were analyzed using Nissl staining and immunohistochemistry for microglial (Iba1) and astrocytic (GFAP) markers. It was found that the signs of neuroinflammation – changes in glial cell morphology and quantity – persist in the perifocal region even 19 days after ischemia induction, despite the small lesion volume. A significant linear relationship between microglial nuclear area and lesion size on day 7 was identified. Conversely, no significant correlation was found between the lesion sizes determined in the hyperacute phase (3 min) and acute phase (1 day) and cellular parameters (cell count, morphometric parameters). This indicates that the lesion formation in the acute phase is dynamic, and only the lesion size after its stabilization influences long-term stroke outcomes. Absence of a correlation between the delayed glial changes and ischemic core size during the hyperacute and acute phases suggests that therapeutic window for interventions modulating glial activity may extend to the later period after stroke, even with small lesion size. The results also allow us to conclude that it is not necessary to make an amendment for the initial lesion size in the studies of delayed neuroglial processes in preclinical models. In turn, the correlation between the lesion size on day 7 and microglial cell nucleus area on day 19 demonstrates that the lesion size at the end of the acute phase may be one of the prognostic factors for effectiveness of the post-stroke therapy.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 4","pages":"588 - 600"},"PeriodicalIF":2.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757192","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":"Functioning of Synaptic Vesicle Pools: Diversity and Organizational Principles","authors":"Chulpan R. Gafurova,&nbsp;Alexey M. Petrov","doi":"10.1134/S0006297926600535","DOIUrl":"10.1134/S0006297926600535","url":null,"abstract":"<p>Presynaptic nerve terminals contain a large number of vesicles filled with neurotransmitters, whose release ensures signal transmission from the presynaptic neuron to the postsynaptic cell. Despite their morphological homogeneity, synaptic vesicles (SVs) are functionally heterogeneous and are organized into distinct groups (pools) that differ in their ability for exocytosis and mobilization, recycling kinetics, and protein composition. In addition to the classic pools – the readily releasable pool (RRP), recycling pool, and reserve pool – other populations have been identified, including spontaneously recycling vesicles, vesicles of resting pool and superpool. Vesicles from different pools engage in different modes of exocytosis and endocytosis, and the extent of interpool mixing varies depending on the synapse type and physiological or pathological conditions. Changes in the organization of SV pools underlie multiple forms of synaptic plasticity. Furthermore, SV cycling is a target of several pharmacological agents, and its disruption plays a significant role in the pathogenesis of neurodegenerative diseases. This article is a systematic review of SV pools, their organizational features in central and peripheral synapses, and implications of changes in the structure of SV pools in synaptic plasticity, action of drugs, and development of neurological disorders.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 4","pages":"561 - 587"},"PeriodicalIF":2.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757191","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":"Cyclophilin A Induces Mechanisms of Cell Rearrangement and Fusion During Differentiation and Maturation of Early Macrophage Precursors","authors":"Anastasiia A. Kalinina,&nbsp;Antonina Yu. Alexandrova,&nbsp;Dmitry B. Kazansky,&nbsp;Ludmila M. Khromykh","doi":"10.1134/S0006297926600523","DOIUrl":"10.1134/S0006297926600523","url":null,"abstract":"<p>Macrophages are a heterogeneous cell population whose functional diversity is formed during their maturation and depends on factors of the microenvironment after their migration into the bloodstream or tissues. One such factor is the pro-inflammatory protein cyclophilin A (CypA, 18 kDa). Using a model of early human monocytic THP-1 cells, it was shown that recombinant human CypA (rhCypA) exerts a differentiating effect on these cells, inducing their maturation, adhesion, and spreading. Under the effect of rhCypA, the THP-1 cells developed an actin cytoskeleton characteristic of motile cells with numerous pseudopodia and podosomes, which ensure tight adhesion of the cells to the substrate and determine their migratory capabilities. Combination of low concentrations of rhCypA and other activators (phorbol myristate acetate) showed an additive effect and ensured effective monocyte differentiation. It was shown that rhCypA, along with other pro-inflammatory factors (IFNγ, TNFα), promotes cell fusion and induces formation of multinucleated macrophages, which are formed during osteoclast maturation under normal conditions as well as during granuloma formation in chronic inflammation (tuberculosis, Crohn’s disease). Multinucleated giant cells have significantly higher functional activity (phagocytosis, bactericidal, and pro-inflammatory activity) compared to the mononuclear forms. The study showed that rhCypA enhances expression of the CD147 molecule, an integral functional regulator of CD29 and CD98 molecules involved in the processes of cell adhesion and fusion. Elevated doses of CypA cause deterioration in macrophages, inducing their apoptosis, which may play a role in regulation of the immune response. The findings of this study determined the mechanisms by which secreted CypA mediates monocyte differentiation and maturation, as well as it showed functional role of macrophages in the development of the immune response, which could facilitate further development of therapeutic approaches for the treatment of infectious, autoimmune, and other diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 4","pages":"612 - 622"},"PeriodicalIF":2.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757193","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":"Effect of Mutations in the N-Terminal Peptide of the Coat Protein on the Structure of Potato Virus X According to Small-Angle X-Ray Scattering and Molecular Dynamics","authors":"Alexander L. Ksenofontov,&nbsp;Maxim V. Petoukhov,&nbsp;Alexander M. Arutyunyan,&nbsp;Ilya P. Oleynikov,&nbsp;Georgy S. Peters,&nbsp;Lyudmila A. Baratova,&nbsp;Marina V. Arkhipenko,&nbsp;Nikolai A. Nikitin,&nbsp;Olga V. Karpova,&nbsp;Eleonora V. Shtykova","doi":"10.1134/S0006297925604472","DOIUrl":"10.1134/S0006297925604472","url":null,"abstract":"<p>Mutations in the N-terminal peptide (Ser-Thr to Ala-Gly substitution) of the coat protein (CP) of potato virus X (PVX-ST) render its genomic RNA translationally competent, unlike in the wild-type PVX virions. Consequently, RNA within the PVX-ST virions can be translated without additional triggers (such as phosphorylation or interaction with the triple gene block 1 protein), unlike the encapsidated RNA of the wild-type virus. Comprehensive structural analysis using molecular dynamics (MD), small-angle X-ray scattering (SAXS), and tritium planigraphy revealed differences in the virion organization. The mutations were shown to increase hydrophobicity and induce partial folding of the N-terminal peptides. This triggers structural rearrangement in the PVX-ST virion: packing density of the coat proteins within the helical capsid is altered. This conclusion is supported by the SAXS data, increased accessibility for tritium labeling of the key CP domains (including the RNA-binding region), and reduced stability against the action of the sodium dodecyl sulfate detergent. The obtained results provide explanation for the mechanism by which the encapsidated RNA of the PVX-ST mutant becomes accessible to ribosomes. This mechanism is associated with structural rearrangement of the N-terminal coat protein peptide and change in the packing density of the helical capsid.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 3","pages":"519 - 530"},"PeriodicalIF":2.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606750","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":"Disruption of Lam Family Sterol Transporters Results in Sporulation Defects in the Yeast Saccharomyces cerevisiae","authors":"Elena D. Surikova,&nbsp;Sergey A. Golyshev,&nbsp;Ekaterina A. Smirnova,&nbsp;Ekaterina A. Bartysh,&nbsp;Dmitry A. Knorre,&nbsp;Fedor F. Severin,&nbsp;Svyatoslav S. Sokolov","doi":"10.1134/S000629792560396X","DOIUrl":"10.1134/S000629792560396X","url":null,"abstract":"<p>The primary role of sterols in the cell is to support plasma membrane function, and for this reason their concentration in this compartment is the highest among all cell membranes. In the yeast <i>Saccharomyces cerevisiae</i>, sterol transport between membranes is mediated by proteins of Osh and Lam families. The Lam1-Lam4 proteins are reported to transport sterols passively from plasmalemma to endoplasmic reticulum. The Lam5-Lam6 proteins transport sterols at the ER interface with vacuoles and mitochondria. Deletion of the <i>LAM</i> family genes does not impair cell growth under standard conditions, which makes their biological role unclear. We hypothesized that the Lam family proteins may play a role in yeast sporulation, as the spore plasma membrane is formed <i>de novo</i> from the ER-derived vesicles, which contain less sterol than the plasma membrane, necessitating sterol transport into the newly forming spore plasma membrane. To test this hypothesis, we generated diploid strains with the <i>LAM1-LAM4</i> and <i>LAM5-LAM6</i> deletions. We demonstrated that double deletion of the <i>LAM5-LAM6</i> genes reduced both percentage of the sporulating cells and number of the spores per ascus. Conversely, deletion of the <i>LAM1-LAM4</i> genes reduced proportion of the full asci but did not inhibit sporulation initiation. We demonstrated that deletion of the <i>LAM1-LAM4</i> genes induces cell wall thickening and structural defects. Clusters of osmiophilic granules were detected at the cell wall surface of these spores. Spores with the deletions of the <i>LAM</i> family genes demonstrated reduced resistance to heat shock and alkali. Taken together, our data indirectly support our hypothesis and point out that sterol transport by the LAM family proteins is necessary for the sterol redistribution during sporulation.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 3","pages":"486 - 498"},"PeriodicalIF":2.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606810","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":"The Structure of the Nucleosomal DNA Repair Intermediate Affects the HPF1-Independent Automodification Activity of PARP2","authors":"Tatyana A. Kurgina,&nbsp;Danil M. Shtanov,&nbsp;Mikhail M. Kutuzov,&nbsp;Nina A. Moor,&nbsp;Olga I. Lavrik","doi":"10.1134/S0006297925603995","DOIUrl":"10.1134/S0006297925603995","url":null,"abstract":"<p>DNA-dependent nuclear enzymes poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2) are involved in the regulation of multiple DNA repair pathways, including base excision repair (BER). After activation by binding to damaged DNA, these enzymes synthesize negatively charged poly(ADP-ribose) (PAR) and covalently attach to amino acid residues of target proteins, including PARPs themselves. PARP2 activity is influenced by the nature of DNA lesion; for example, it is efficiently stimulated by DNA breaks flanked by phosphate group. However, it remains unclear which stages of the auto-PARylation reaction are most sensitive to the structure of damaged DNA. In this study, we investigated how PARP2 activity depends on the presence and position of a single-nucleotide gap in DNA (either free or in the context of nucleosome) at different stages of the automodification reaction conducted in the absence of the histone PARylation factor HPF1. The obtained results suggest that the presence of the gap affects the affinity of PARP2 for DNA/nucleosomes, thereby determining the number of catalytically active enzyme molecules and the efficiency of PARylation initiation. In contrast, PAR elongation was affected by the lesion location in the DNA/nucleosome structure, namely, its distance from the blunt DNA ends, and the environment of histone tails. Therefore, the damaged DNA structure can influence both the amount and the length of PAR synthesized by PARP2.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 3","pages":"499 - 510"},"PeriodicalIF":2.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606730","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":"Epigallocatechin Gallate as an Anti-Fibrotic Agent","authors":"Yury S. Tarahovsky,&nbsp;Sergey G. Gaidin,&nbsp;Yury A. Kim","doi":"10.1134/S0006297925603715","DOIUrl":"10.1134/S0006297925603715","url":null,"abstract":"<p>Epigallocatechin gallate (EGCG), a major polyphenolic compound in green tea, exhibits preventive and therapeutic effects in many fibrotic diseases. Tissue fibrosis is characterized by excessive deposition of collagen fibrils in the extracellular matrix, primarily due to dysregulation of cellular signaling pathways. However, we have previously demonstrated that EGCG directly inhibits the formation of collagen fibrils from collagen monomers under <i>in vitro</i> experimental conditions that excluded involvement of cellular signaling systems. This review explores the antifibrotic action of EGCG, which may occur through (i) its influence on cellular signaling and (ii) direct binding to collagen monomers, leading to the inhibition of pathological fibrillogenesis, as well as discuss the prospects for targeting the collagen assembly process.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 3","pages":"432 - 447"},"PeriodicalIF":2.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606809","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":"Two-Stage Purification of Recombinant Antibodies Using Non-Ionic Detergent Prevents Endotoxin-Induced Macrophage Activation: The Case of Bispecific Mini-Antibody MYSTI-2","authors":"Yuliya A. Khodak,&nbsp;Anna M. Litvinova,&nbsp;Fedor A. Sysonov,&nbsp;Marina S. Drutskaya,&nbsp;Irina V. Safenkova,&nbsp;Sergei A. Nedospasov,&nbsp;Ivan I. Vorobiev","doi":"10.1134/S0006297926600225","DOIUrl":"10.1134/S0006297926600225","url":null,"abstract":"<p><i>Escherichia coli</i> is one of the most common producers of recombinant proteins, including therapeutic antibody fragments. However, the outer membrane of <i>E. coli</i> contains high levels of lipopolysaccharide (LPS, also known as endotoxin), which can activate innate immune receptors, trigger immune responses, and induce systemic inflammation that may progress to septic shock. Ensuring extremely low endotoxin levels in preparations intended for <i>in vivo</i> applications is critically important. In this study, we investigated the endotoxin content in preparations of the bispecific mini-antibody MYSTI-2 produced in two <i>E. coli</i> strains: the Rosetta strain, which synthesizes conventional LPS, and the ClearColi strain, which synthesizes potentially non-toxic form of LPS. Our results demonstrate that near-complete removal of LPS can be achieved only through the use of a non-ionic detergent during purification, regardless of the bacterial strain used for protein production.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 3","pages":"531 - 542"},"PeriodicalIF":2.2,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147606876","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}