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

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Functional Role of Piezo1 Channels in Smooth Muscle Cells of Rat Cerebral Arteries under Normal Conditions and Chronic Carotid Artery Stenosis 正常及慢性颈动脉狭窄大鼠脑动脉平滑肌细胞中Piezo1通道的功能作用
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S1990747825700552
D. K. Gaynullina, A. A. Borzykh, M. G. Pechkova, K. A. Bogotskoy, O. S. Tarasova
{"title":"Functional Role of Piezo1 Channels in Smooth Muscle Cells of Rat Cerebral Arteries under Normal Conditions and Chronic Carotid Artery Stenosis","authors":"D. K. Gaynullina,&nbsp;A. A. Borzykh,&nbsp;M. G. Pechkova,&nbsp;K. A. Bogotskoy,&nbsp;O. S. Tarasova","doi":"10.1134/S1990747825700552","DOIUrl":"10.1134/S1990747825700552","url":null,"abstract":"<p>In arterial smooth muscle cells, Piezo1 channels are involved in the regulation of vascular tone and remodeling in various diseases. They are non-selective cation channels, the activation of which can lead to depolarization of the smooth muscle cell membrane, Ca<sup>2+</sup> entry through voltage-gated channels and the development of contraction. This work tested the hypothesis that Piezo1 channels are involved in regulating the tone of smooth muscle cells in small cerebral arteries, and functional contribution of these channels may change in chronic carotid artery stenosis. Constricting clips were placed on both common carotid arteries in rats (reducing the volume velocity of blood flow by at least 70%). After 4 weeks, the middle cerebral artery (MCA) was isolated for wire myography (after endothelial removal) and quantitative PCR. The level of MCA basal tone was lower in the rats of the Stenosis group than in the control group; contractile responses to thromboxane A2 receptor agonist U46619 were not changed. Incubation with Dooku1 (Piezo1 blocker, 30 µM) led to decreases in basal tone level and contractile responses to U46619 in MCA of control rats but did not have such effects in MCA of the Stenosis group. The contents of Piezo1 and voltage-gated L-type Ca<sup>2+</sup> channel (Ca<sub>V</sub>1.2) mRNAs did not differ between the groups, whereas the mRNA content of voltage-gated Ca<sup>2+</sup> channels of the T type (Ca<sub>V</sub>3.1) was decreased in the MCA of the Stenosis group compared to the control. Thus, Piezo1 channels have a pro-contractile effect in the smooth muscle cells of rat cerebral arteries, and this effect decreases with chronic stenosis of carotid artery. The decrease in the pro-contractile effect of Piezo1 in the MCA of rats of the Stenosis group may be associated with the development of changes not at the level of the Piezo1 channels themselves, but at subsequent stages of signal transduction to the contractile apparatus of smooth muscle cells.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"39 - 46"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099193","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}
引用次数: 0
Resistance of CD33+ Acute Myeloid Leukemia Cells to Anthracyclines in Three-Dimensional Cultures 三维培养CD33+急性髓系白血病细胞对蒽环类药物的耐药性
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S1990747825700564
K. S. Krasnov, E. I. Meshcheriakova, Ya. V. Lomovskaya, I. S. Fadeeva, M. I. Kobyakova, R. S. Fadeev
{"title":"Resistance of CD33+ Acute Myeloid Leukemia Cells to Anthracyclines in Three-Dimensional Cultures","authors":"K. S. Krasnov,&nbsp;E. I. Meshcheriakova,&nbsp;Ya. V. Lomovskaya,&nbsp;I. S. Fadeeva,&nbsp;M. I. Kobyakova,&nbsp;R. S. Fadeev","doi":"10.1134/S1990747825700564","DOIUrl":"10.1134/S1990747825700564","url":null,"abstract":"<p>Elucidating the mechanisms of drug resistance in acute myeloid leukemia (AML) cells is a critical endeavor in biomedicine and oncohematology. In our previous research utilizing permanent cell lines, we demonstrated that AML cells in three-dimensional multicellular cultures exhibited increased drug resistance. This study utilized flow cytometry and spectrofluorometry to demonstrate enhanced resistance of primary CD33+ AML cells, cultured in three-dimensional multicellular aggregates, to the cytotoxic effects of anthracyclines. This resistance was associated with the inhibition of the pro-apoptotic signaling pathway, a partial accumulation of cells in the G0/G1 phase of the cell cycle, and an elevation in the levels of the anti-apoptotic protein Bcl-2.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"47 - 58"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099026","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}
引用次数: 0
The Dominance of Intracellular Maturation of Brain-Derived Neurotrophic Factor Ensures Its Retrograde Effect in Newly Formed Mouse Motor Synapses 脑源性神经营养因子在细胞内成熟的优势保证了其在新形成的小鼠运动突触中的逆行作用
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S1990747825700539
P. O. Bogacheva, D. A. Potapova, A. E. Gaydukov
{"title":"The Dominance of Intracellular Maturation of Brain-Derived Neurotrophic Factor Ensures Its Retrograde Effect in Newly Formed Mouse Motor Synapses","authors":"P. O. Bogacheva,&nbsp;D. A. Potapova,&nbsp;A. E. Gaydukov","doi":"10.1134/S1990747825700539","DOIUrl":"10.1134/S1990747825700539","url":null,"abstract":"<p>Miniature endplate potentials (MEPPs) and multiquantal endplate potentials (EPPs) caused by short rhythmic nerve stimulation were recorded in newly formed neuromuscular synapses of mice using intracellular microelectrode technique. In this work, we investigated which pathway of maturation of mature brain-derived neurotrophic factor (BDNF) from its precursor proBDNF dominates in muscle fibers during their reinnervation—extracellular or intracellular. Matrix metalloprotease 3 (MMP-3) or intracellular proconvertase furin were selectively inhibited in combination with the release of endogenous neurotrophin from muscle fibers upon stimulation of protease-activated receptors (PAR1). It was confirmed that PAR1 stimulation causes an increase in the amplitude of MEPPs due to the release of endogenous BDNF from muscle fibers and its retrograde effect aimed at increasing the quantal size of the acetylcholine (ACh). MMP-3 does not participate in the maturation of BDNF. Inhibition of furin led to a change in the synaptic effect upon stimulation of PAR1. An increase in the amplitude of MEPPs upon activation of PAR1 changes to a decrease in the frequency of MEPPs, which is characteristic of the effect of proBDNF in newly formed synapses. Thus, it has been shown that it is possible to stop the maturation of muscle BDNF by inhibiting the activity of furin at the stage of proneurotrophin in weakened regenerating synapses and eventually ensure the appearance of proBDNF in the synaptic cleft with its spectrum of effects. This may change the balance of the retrograde effect of BDNF and its proneurotrophin on the functioning of newly formed motor synapses. Moreover, a change in this balance can potentially affect not only the regulation of quantal ACh release, but also the rate and severity of reinnervation, since BDNF and proBDNF have a multidirectional effect on the elimination of excessive synaptic contacts in embryogenesis and post-traumatic muscle reinnervation.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"17 - 28"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099190","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}
引用次数: 0
Effect of the Combination of TGFβ + MCSF + Cholesterol on the Percentage and Functional Activity of Microglia in Rat Hippocampal Cell Cultures tgf - β + MCSF +胆固醇对大鼠海马细胞培养小胶质细胞百分比和功能活性的影响
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S199074782570059X
V. N. Mal’tseva, I. A. Tumozov, N. A. Ryndina, A. M. Kosenkov, S. G. Gaidin
{"title":"Effect of the Combination of TGFβ + MCSF + Cholesterol on the Percentage and Functional Activity of Microglia in Rat Hippocampal Cell Cultures","authors":"V. N. Mal’tseva,&nbsp;I. A. Tumozov,&nbsp;N. A. Ryndina,&nbsp;A. M. Kosenkov,&nbsp;S. G. Gaidin","doi":"10.1134/S199074782570059X","DOIUrl":"10.1134/S199074782570059X","url":null,"abstract":"<p>Microglia cells in the brain are considered resident macrophages possessing a number of functional and physiological characteristics typical of these immune cells. Microglia are involved in neuroinflammatory processes of various etiologies, during which they undergo phenotypic changes. In neuron-glial cultures, microglial cells typically have low proliferative capacity due to the absence of necessary growth factors. In this study, we evaluated the effect of a combination of compounds critical for microglial proliferation, such as transforming growth factor beta (TGFβ), macrophage colony-stimulating factor (MCSF), and cholesterol, on the number and functional activity of microglial cells in hippocampal cultures from newborn rats. We found that the combination TGFβ + MCSF + cholesterol increased the number of microglial cells in cultures by more than twofold. RT-PCR analysis showed that exposure to the pro-inflammatory agent lipopolysaccharide (LPS) in cultures grown using this combination of factors led to increased expression of genes encoding inflammation-associated proteins, such as IL-1β, TNFα, STAT3, as well as the gene encoding protein vimentin, which acts as a situational marker of reactive microglia. Additionally, incubation with LPS led to increased cell death in the cultures. In the case of hypoxic episode exposure, expression of genes encoding the mentioned pro-inflammatory proteins was suppressed, while the increase in cell death was insignificant. LPS, as well as chemotactic formylated peptide (fMLP, an immune cell activator), caused enhanced production of superoxide anion and increased intracellular Ca<sup>2+</sup> concentration in microglial cells. Thus, the described effects of LPS may indicate that the combination TGFβ + MCSF + cholesterol added to the culture medium promotes the preservation and proliferation of functionally active microglial cells in neuron-glial cultures.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"78 - 88"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099089","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}
引用次数: 0
Post-translational Modifications of Proteins with Disordered Structure in the Regulation of Regeneration and Neurodegeneration of Brain Cells 结构紊乱蛋白在脑细胞再生和神经变性调控中的翻译后修饰
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S1990747825700515
S. V. Demyanenko, A. M. Khaitin, S. A. Batalshchikova
{"title":"Post-translational Modifications of Proteins with Disordered Structure in the Regulation of Regeneration and Neurodegeneration of Brain Cells","authors":"S. V. Demyanenko,&nbsp;A. M. Khaitin,&nbsp;S. A. Batalshchikova","doi":"10.1134/S1990747825700515","DOIUrl":"10.1134/S1990747825700515","url":null,"abstract":"<p>This review focuses on the role of intrinsically disordered proteins and their post-translational modifications in the regulation of neuronal regeneration and neurodegeneration processes. Intrinsically disordered proteins, with their high conformational flexibility and lack of stable tertiary structure, can participate in a variety of cellular processes through dynamic and specific interactions with various partners. They are involved in the regulation of transcription, apoptosis, cell cycle, and stress responses. Key examples of such proteins are the transcription factors p53, c-Myc, FOXO3a, and E2F1, which, depending on the set of post-translational modifications, can switch between the functions of protecting neurons and activating their death. Particular attention is paid to the mechanisms by which post-translational modifications, such as acetylation, phosphorylation, and ubiquitination, alter the localization, stability, and activity of intrinsically disordered proteins affecting the outcome of cell fate. The contribution of misfolded proteins with structurally disordered domains, such as Tau and α-synuclein, to the pathogenesis of neurodegenerative diseases is also discussed. The article highlights the challenges associated with therapeutic targeting of such proteins due to their structural plasticity and diversity of post-translational modifications. Promising approaches to modulating the overall activity and functional state of target proteins are discussed, including modulation of the activity of post-translational modification enzymes and proteostasis mechanisms. The review illustrates the critical need for a comprehensive study of post-translational modifications as mechanisms of the disordered protein regulation for the development of new strategies for the treatment of acute nerve cell damage and neurodegenerative diseases.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"1 - 8"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099090","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}
引用次数: 0
The Potential for Using the Mechanism of Hypoxic Adaptation in Lower Eukaryotes 利用低氧适应机制在低等真核生物中的潜力
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S1990747825700527
D. B. Zorov, L. D. Zorova, V. A. Babenko, D. S. Semenovich, A. E. Ivanova, S. D. Zorov, I. B. Pevzner, E. Y. Plotnikov, D. N. Silachev, G. T. Sukhikh
{"title":"The Potential for Using the Mechanism of Hypoxic Adaptation in Lower Eukaryotes","authors":"D. B. Zorov,&nbsp;L. D. Zorova,&nbsp;V. A. Babenko,&nbsp;D. S. Semenovich,&nbsp;A. E. Ivanova,&nbsp;S. D. Zorov,&nbsp;I. B. Pevzner,&nbsp;E. Y. Plotnikov,&nbsp;D. N. Silachev,&nbsp;G. T. Sukhikh","doi":"10.1134/S1990747825700527","DOIUrl":"10.1134/S1990747825700527","url":null,"abstract":"<p>This analytical review considers the main elements of mitochondrial restructuring that occurs in eukaryotes forced to live in hypoxic conditions for a long time. In these organisms, mitochondria retain their activity, not only synthetic and signaling, but also bioenergetic, albeit to a lesser extent. The reorganization, primarily accompanied by the reversal of the succinate dehydrogenase reaction and the presence of low-potential quinone, allows organisms to obtain energy exclusively from complex I in mitochondria. A comprehensive review of all changes caused by constant exposure to hypoxic conditions allows us to develop an anti-hypoxic strategy that eliminates the influence of undesirable factors associated with hypoxic changes. On the other hand, understanding all elements of hypoxia-induced changes makes it possible to use them in combating solid tumor cells that live in the oxygen-deprived microenvironment.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"9 - 16"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099191","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}
引用次数: 0
Activation of Pyruvate Dehydrogenase Complex with Inhibition of Krebs Cycle and Mitochondrial Respiration by the Excess of Pyruvate 丙酮酸过量激活丙酮酸脱氢酶复合物,抑制克雷布斯循环和线粒体呼吸
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S1990747825700540
V. V. Dynnik, E. V. Grishina, N. I. Fedotcheva
{"title":"Activation of Pyruvate Dehydrogenase Complex with Inhibition of Krebs Cycle and Mitochondrial Respiration by the Excess of Pyruvate","authors":"V. V. Dynnik,&nbsp;E. V. Grishina,&nbsp;N. I. Fedotcheva","doi":"10.1134/S1990747825700540","DOIUrl":"10.1134/S1990747825700540","url":null,"abstract":"<p>Experiments on isolated rat liver mitochondria have shown that pyruvate (10–30 mM) in the presence of <i>L</i>-glutamate causes concentration-dependent inhibition of respiration activated by ADP. Respiration is reactivated by 3 mM of <i>L</i>-malate. Both effects are reproduced in the presence of <i>D</i>, <i>L</i>-acetylcarnitine (AcCar), which indicates the important role of acetylCoA (AcCoA) in the regulation of Krebs cycle reactions. When pyruvate is oxidized, the respiration rate decreases within a few hundred seconds. The effect is reproduced in the presence of dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), and is not observed with excess AcCar, indicating dephosphorylation of pyruvate dehydrogenase (PDH) when PDK is inhibited by pyruvate (+ADP) or DCA. The effects of pyruvate and AcCar depend on the preincubation duration of mitochondria in state 2. Experiments on frozen/thawed mitochondria show that preincubation of mitochondria with pyruvate restores PDH activity and suppresses the activity of α-ketoglutarate dehydrogenase (α-KGDH) detected by NADH fluorescence. Thus, a possible mechanism of the respiration inhibition by pyruvate is a mechanism combining (1) allosteric inhibition of citrate synthase by the excess of AcCoA at low concentrations of oxaloacetate and α-KGDH with the possible participation of acetoacetylCoA and (2) slow acetylation of α-KGDH and other cycle enzymes by the excess of AcCoA during slow reactivation of PDH by pyruvate.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"29 - 38"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099195","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}
引用次数: 0
Morphological and Functional Evaluation of Rat Leg Muscles under the Influence of Hindlimb Unloading, Tenotomy, and Denervation 后肢卸甲、断腱和去神经对大鼠腿部肌肉形态和功能的影响
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S1990747825700606
D. E. Sabirova, A. A. Shadrina, A. A. Eremeev, A. E. Khairullin, T. V. Baltina
{"title":"Morphological and Functional Evaluation of Rat Leg Muscles under the Influence of Hindlimb Unloading, Tenotomy, and Denervation","authors":"D. E. Sabirova,&nbsp;A. A. Shadrina,&nbsp;A. A. Eremeev,&nbsp;A. E. Khairullin,&nbsp;T. V. Baltina","doi":"10.1134/S1990747825700606","DOIUrl":"10.1134/S1990747825700606","url":null,"abstract":"<p>Skeletal muscle atrophy can develop under the influence of various factors associated with their disuse, such as immobilization, denervation, or exposure to microgravity. The aim of the study was to conduct a morphological and functional assessment of the soleus, gastrocnemius, and tibialis anterior muscles in models of disuse in rats. The rats were randomly divided into a control group and groups subjected to denervation, tenotomy, and hindlimb unloading (HU). During the experiments, a decrease in muscle fiber diameter was observed in all experimental groups. Tenotomy resulted in a decrease in dystrophin immunoexpression. With HU, the level of dystrophin decreased, but by day 35, recovery was observed in the gastrocnemius and tibialis anterior muscles, while in the soleus muscle, the level continued to fall. After denervation, the dystrophin content also decreased but then increased, reaching control values in the soleus muscle by day 35. The level of neuronal NO synthase decreased significantly in all experimental groups. Denervation and tenotomy lead to pronounced changes in the contractile function of the soleus muscle in rats.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"89 - 102"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099091","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}
引用次数: 0
Activation of FLT3-Associated Signaling Pathways in Quizartinib-Resistant Macrophage-Like Cells of Acute Myeloid Leukemia 急性髓系白血病抗quizarinib巨噬细胞样细胞flt3相关信号通路的激活
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S1990747825700588
Ya. V. Lomovskaya, M. I. Kobyakova, K. S. Krasnov, A. I. Lomovsky, E. I. Meshcheriakova, R. S. Fadeev
{"title":"Activation of FLT3-Associated Signaling Pathways in Quizartinib-Resistant Macrophage-Like Cells of Acute Myeloid Leukemia","authors":"Ya. V. Lomovskaya,&nbsp;M. I. Kobyakova,&nbsp;K. S. Krasnov,&nbsp;A. I. Lomovsky,&nbsp;E. I. Meshcheriakova,&nbsp;R. S. Fadeev","doi":"10.1134/S1990747825700588","DOIUrl":"10.1134/S1990747825700588","url":null,"abstract":"<p>Investigating the mechanisms of resistance of acute myeloid leukemia (AML) cells to anticancer therapy, including targeted drugs such as the FLT3 inhibitor quizartinib, remains highly relevant in modern molecular oncology. In this work, we explored the mechanisms underlying quizartinib resistance in macrophage-like THP-1ad cells. We demonstrated that resistance is associated with downregulation of the expression of the FLT3 receptor due to suppressed FLT3 gene transcriptional activity, while key downstream signaling pathways (STAT5, PI3K/AKT, ERK) remain functionally active. The findings indicate that resistance to FLT3 inhibitors in AML cells may develop independently of classical mutational mechanisms, but rather through alternative activation of signaling cascades. These results expand current understanding of resistance mechanisms in AML and support the rationale for targeting signaling pathways downstream of FLT3 as a promising strategy to overcome resistance in tumor cells refractory to FLT3 inhibitors.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"69 - 77"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099192","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}
引用次数: 0
Decompensated Liver Cirrhosis Impairs the Deformability of Erythrocytes and Their Ability to Pass Through Microchannels 失代偿性肝硬化损害红细胞的变形能力及其通过微通道的能力
IF 1.4
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2026-02-02 DOI: 10.1134/S1990747825700618
E. A. Skverchinskaya, O. I. Filippova, S. P. Gambaryan, A. S. Bukatin, A. V. Koloskov, I. V. Mindukshev
{"title":"Decompensated Liver Cirrhosis Impairs the Deformability of Erythrocytes and Their Ability to Pass Through Microchannels","authors":"E. A. Skverchinskaya,&nbsp;O. I. Filippova,&nbsp;S. P. Gambaryan,&nbsp;A. S. Bukatin,&nbsp;A. V. Koloskov,&nbsp;I. V. Mindukshev","doi":"10.1134/S1990747825700618","DOIUrl":"10.1134/S1990747825700618","url":null,"abstract":"<p>Red blood cells (RBC, erythrocytes) are the main cell population that ensures tissue oxygenation and forms the ordered movement of all blood cells through the vessels. Disturbances in the physiological deformability of red blood cells aggravate the degree of anemia in two ways: aberrant red blood cells are rapidly eliminated by sequestration and destruction in the spleen and liver; and second, poorly deformable red blood cells have a reduced potential for gas exchange in the capillaries due to a decrease in the membrane contact area. Regardless of the etiology of hepatosis, liver cirrhosis (LC) develops persistent anemia, but disorders of erythrocyte deformability in patients with decompensated liver cirrhosis have been poorly studied. Using laser diffraction, flow cytometry, and microfluidic analysis, we showed that erythrocytes of LC patients develop disorders of deformability caused by the stress type of erythropoiesis (release of immature reticulocytes into circulation, an increase in the proportion of phosphatidylserine-presenting erythrocytes, a decrease in the activity of cytosolic esterases. In LC, erythrocytes have a pronounced rigidity to hypoosmotic load: induced hemolysis is incomplete, its speed is reduced, which indicates a decrease in the deformability of erythrocytes. Deformability disorders affected the ability of erythrocytes to pass through microchannels - the transit velocity was decreased, a high percentage of occlusions was observed, i.e., signs of microrheology disorders were identified. A connection was established between the disorders of erythrocyte microrheology depending on the degree of LC progression.</p>","PeriodicalId":484,"journal":{"name":"Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology","volume":"20 Receptors","pages":"103 - 117"},"PeriodicalIF":1.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099088","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}
引用次数: 0
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