Biochemistry (Moscow)最新文献_第2页

Dynamics of Expression of the Neuronal Markers MAP2 and N200 in Human Brain Tissue during Early Gestation 妊娠早期人脑组织中神经元标记物MAP2和N200的表达动态

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-10-02 DOI: 10.1134/S0006297926601024

Sofia N. Shumilova, Aleksey V. Potapov, Anatoly V. Solonsky, Timur A. Shageev, Elena Yu. Varakuta, Alexander V. Gerasimov

{"title":"Dynamics of Expression of the Neuronal Markers MAP2 and N200 in Human Brain Tissue during Early Gestation","authors":"Sofia N. Shumilova, Aleksey V. Potapov, Anatoly V. Solonsky, Timur A. Shageev, Elena Yu. Varakuta, Alexander V. Gerasimov","doi":"10.1134/S0006297926601024","DOIUrl":"10.1134/S0006297926601024","url":null,"abstract":"The article presents the results of investigation of the cerebral wall layer cytoarchitecture, overall cell density, and expression of neuronal markers N200 and MAP2 in human fetuses (n = 20) at early gestational stages (8-11 completed weeks). At 8 week of embryogenesis, the telencephalic wall consisted of the ventricular, intermediate, and marginal zones. By week 10, the subventricular zone, subplate, and cortical plate had formed; however, no distinct cortical layering was observed at this stage. The developing neural tissue demonstrated wave-like changes in cell density. Active proliferation, reflected by the highest density of DAPI-positive nuclei, was recorded at week 8, followed by regression with a decline in cell numbers by week 9 and a partial recovery of the cell pool by weeks 10-11. A similar trend was observed for the relative proportion of N200-positive cells, a marker of developing corticofugal neurons. The proportion of N200-positive cells was highest at 8 weeks of gestation, decreased significantly by week 10, and increased again by week 11. In contrast, no changes in the dynamics of synaptogenesis were revealed, as assessed by the area occupied by MAP2-positive structures, which remained stable at all studied time points, with no significant intergroup differences. The distribution of this marker in the intermediate zone and its absence in the ventricular and marginal zones from week 8 indicated an early onset of dendritic differentiation of neuroblasts during radial migration, before their final positioning in the cortical plate.","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1566 - 1573"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098211","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}

引用次数: 0

Roles of Mitochondrial Genome-Encoded Circular RNAs (mecciRNAs) in Human Diseases: Potential Biomarkers and Therapeutic Targets 线粒体基因组编码环状rna （mecciRNAs）在人类疾病中的作用：潜在的生物标志物和治疗靶点

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-10-02 DOI: 10.1134/S0006297926601668

Zahra Firoozi, Abbas Shahi, Mohammadreza Sharifi, Ali Moravej, Saeed Mohammadi, Abdolreza Daraei, Hassan Dastsooz, Yaser Mansoori, Rasoul Salehi

{"title":"Roles of Mitochondrial Genome-Encoded Circular RNAs (mecciRNAs) in Human Diseases: Potential Biomarkers and Therapeutic Targets","authors":"Zahra Firoozi, Abbas Shahi, Mohammadreza Sharifi, Ali Moravej, Saeed Mohammadi, Abdolreza Daraei, Hassan Dastsooz, Yaser Mansoori, Rasoul Salehi","doi":"10.1134/S0006297926601668","DOIUrl":"10.1134/S0006297926601668","url":null,"abstract":"Generation of energy and maintenance of homeostasis in eukaryotic cells depends on organelles known as mitochondria, which have their own circular genomes and take part in a number of metabolic activities and cellular events. Bioinformatics techniques and RNA-sequencing (RNA-seq) have helped unravel intricacy of the transcripts originating from mitochondria. Numerous mitochondrial noncoding RNAs (mt-ncRNAs) have been identified in the recent studies, and they are crucial for both mitochondrial and other cellular processes. According to the recently published research, circular RNAs (circRNAs) are endogenous macromolecules with covalent closure at the 5’ and 3’ ends, which are one of the novel subtypes of ncRNAs. CircRNAs are mostly found in the cytoplasm and nucleus, although this kind of ncRNA can also be detected in mitochondria. Mitochondrial genome-encoded circular RNAs (mecciRNAs) play key roles in regulating cellular phenotypes and progressive illness by sponging microRNA (miRNA) and interacting with the RNA binding proteins (RBP). In this review, we focus on the recent research on the regulatory mechanism and possible functions of mecciRNAs in pathophysiology of various diseases.","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1481 - 1506"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098400","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}

引用次数: 0

Dynamics of Orthoflavivirus Reproduction and Cytokine Responses in the A549ACE2 and HEK-293T Cells 原黄病毒在A549ACE2和HEK-293T细胞中的繁殖动态和细胞因子反应

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-10-02 DOI: 10.1134/S0006297926601681

Ksenia Tuchynskaya, Ivan Kholodilov, Ilia Kruglov, Vladimir Chulanov, Dmitry Kostyushev, Galina Karganova

{"title":"Dynamics of Orthoflavivirus Reproduction and Cytokine Responses in the A549ACE2 and HEK-293T Cells","authors":"Ksenia Tuchynskaya, Ivan Kholodilov, Ilia Kruglov, Vladimir Chulanov, Dmitry Kostyushev, Galina Karganova","doi":"10.1134/S0006297926601681","DOIUrl":"10.1134/S0006297926601681","url":null,"abstract":"Orthoflaviviruses circulating in the Russian Federation that include the tick-borne encephalitis virus (TBEV), the Powassan virus (POWV), the Omsk hemorrhagic fever virus (OHFV), and the West Nile virus (WNV) are of significant concern. Development of a suitable in vitro model is crucial for studying mechanisms of viral replication and immune response to the infection. In the present study, A549ACE2 and HEK-293T cells widely employed in biotechnology and biomedicine were used. Dynamics of the infectious and non-infectious viral particle accumulation and production kinetics of the IFN-α, IFN-γ, TNF-α, IL-6, IL-8, IL-10, IL-4, and IL-18 cytokines in these cells at different infectious doses of the viruses were studied. Notably, only WNV caused a cytopathic effect in the cells, which was observed starting 48 h postinfection with a high dose of the virus. The cells showed similar dynamics of multiplication of the studied orthoflaviviruses, which depended on the dose of infectious virus. As expected, the HEK-293T cells exhibited deficiency in the immune response: production of only a low level of IFN-α was observed in response to the WNV infection and decrease in the IL-8 level was detected in response to infection with all studied orthoflaviviruses. In contrast, the A549ACE2 cells demonstrated presence of the IFN-α, TNF-α, IL-6, IL-18, and anti-inflammatory IL-4 cytokines after infection. Furthermore, the detected levels and timing of cytokine production depended on both the virus and the viral dose.","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1615 - 1628"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098403","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}

引用次数: 0

Celastrol Sensitizes Bladder Cancer to Gemcitabine by Regulating LINC00839-Mediated Homologous Recombination DNA Repair Celastrol通过调节linc00839介导的同源重组DNA修复使膀胱癌对吉西他滨致敏

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-10-02 DOI: 10.1134/S0006297926601292

Bo Wei, Tao Liu, Xueshui Chang, Liang Guo, Xu Liu, Zunxian Wang

{"title":"Celastrol Sensitizes Bladder Cancer to Gemcitabine by Regulating LINC00839-Mediated Homologous Recombination DNA Repair","authors":"Bo Wei, Tao Liu, Xueshui Chang, Liang Guo, Xu Liu, Zunxian Wang","doi":"10.1134/S0006297926601292","DOIUrl":"10.1134/S0006297926601292","url":null,"abstract":"Gemcitabine resistance remains a major obstacle in the treatment of advanced bladder cancer. Celastrol, a bioactive triterpenoid derived from traditional Chinese medicinal plants, has been reported to enhance chemosensitivity in multiple malignancies. However, the molecular mechanisms by which celastrol modulates gemcitabine response in bladder cancer remain largely unclear. Human bladder cancer cell lines (T24 and J82) and a gemcitabine-resistant T24 model (T24GEM) were used to investigate the chemosensitizing effects of celastrol. Cell proliferation, colony formation, and drug sensitivity were evaluated in vitro, while a xenograft mouse model was used for in vivo validation. DNA damage and repair were assessed by γH2AX immunofluorescence and homologous recombination (HR) reporter assays. Celastrol significantly enhanced the sensitivity of bladder cancer cells to gemcitabine and suppressed tumor growth. Mechanistically, celastrol downregulated the oncogenic long non-coding RNA LINC00839, leading to inhibition of ATR/CHK1 signaling and impairment of HR-mediated DNA repair. Although the miR-142/SOX5 axis was responsive to celastrol, it was not the primary mediator of chemosensitization. In contrast, activation of the LINC00839-dependent ATR/CHK1 pathway was required for efficient HR-mediated DNA repair and gemcitabine resistance. Pharmacological inhibition of CHK1 phenocopied the effects of celastrol and acted synergistically with gemcitabine. In conclusion, LINC00839–ATR/CHK1–HR repair axis is a key driver of gemcitabine resistance in bladder cancer. Celastrol sensitizes bladder cancer cells to gemcitabine by targeting this pathway, highlighting LINC00839 and ATR/CHK1 as promising therapeutic targets for overcoming chemoresistance.","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1704 - 1715"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098225","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}

引用次数: 0

Investigation of the Nature of the Excited-State of the Primary Electron Donor in the Purple Bacterial Reaction Centers: Femtosecond Absorption Spectroscopy of a Cereibacter sphaeroides Mutant with Blocked Electron Transfer 紫色细菌反应中心初级电子供体激发态性质的研究：一个电子转移受阻的球形Cereibacter sphaeroides突变体的飞秒吸收光谱

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-10-02 DOI: 10.1134/S0006297926601383

Anton M. Khristin, Tatiana Yu. Fufina, Ravil A. Khatypov

{"title":"Investigation of the Nature of the Excited-State of the Primary Electron Donor in the Purple Bacterial Reaction Centers: Femtosecond Absorption Spectroscopy of a Cereibacter sphaeroides Mutant with Blocked Electron Transfer","authors":"Anton M. Khristin, Tatiana Yu. Fufina, Ravil A. Khatypov","doi":"10.1134/S0006297926601383","DOIUrl":"10.1134/S0006297926601383","url":null,"abstract":"Using femtosecond transient absorption spectroscopy, we investigated dynamics of absorption changes in the mutant reaction centers (RCs) of Cereibacter (C.) sphaeroides harboring the amino acid substitutions M160LH+L131LH+M197FH and M210YL, a combination known to block photoinduced charge separation. In these mutant RCs, formation of a long-lived excited state of the primary electron donor (P*) was observed. This state is characterized by stimulated emission that is red-shifted by 20 nm relative to that in the wild-type RCs. We hypothesize that the excited special-pair dimer adopts a charge-transfer state, (PAδ+PBδ−)*, which becomes long-lived under conditions where electron transfer is blocked in the mutant RC. On the energy scale, our data place the (PAδ+PBδ−)* state approximately 20 meV below the excitonic P* level. Within this framework, in the native RCs, the (PAδ+PBδ−)* charge-transfer state is short-lived and participates in ultrafast coherent electron-transfer reactions to the BA acceptor.","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1574 - 1586"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098212","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}

引用次数: 0

13/16-Specific Allene Oxide Synthase BnAOS (CYP74A) of Rapeseed (Brassica napus L.): Identification and Biochemical Properties 油菜（Brassica napus L.） 13/16特异性烯氧化物合成酶BnAOS (CYP74A)：鉴定及生化特性

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-10-02 DOI: 10.1134/S0006297926602650

Svetlana S. Gorina, Natalia V. Lantsova, Yana Y. Toporkova

{"title":"13/16-Specific Allene Oxide Synthase BnAOS (CYP74A) of Rapeseed (Brassica napus L.): Identification and Biochemical Properties","authors":"Svetlana S. Gorina, Natalia V. Lantsova, Yana Y. Toporkova","doi":"10.1134/S0006297926602650","DOIUrl":"10.1134/S0006297926602650","url":null,"abstract":"Lipoxygenase cascade is the source of key plant bioregulators, oxylipins, which are oxidized derivatives of polyunsaturated fatty acids that play a crucial role in growth and development, as well as stress response. The key enzymes of the lipoxygenase cascade are allene oxide synthases (AOS) and hydroperoxide lyases, which are present in all known angiosperms. Although these enzymes play a central role in defining the pattern of the final metabolites of the cascade, significant gaps still exist in understanding their catalytic properties and positional specificity. This paper describes the allene oxide synthase BnAOS from rapeseed (Brassica napus L.), an important agricultural crop and source of valuable rapeseed oil. The BnAOS enzyme belongs to the CYP74A subfamily, which traditionally includes 13-specific allene oxide synthases. However, some members of this group are universal and capable of converting both 13- and 9-hydroperoxides of linoleic and α-linolenic acids. Thus, they direct the biosynthesis of oxylipins towards formation of jasmonates (in the case of conversion of (13S)-hydroperoxide of α-linolenic acid) or other metabolites when using other hydroperoxides as substrates. Our studies have shown that the BnAOS also exhibits dual positional specificity, but, in addition to 13-hydroperoxides, it efficiently converts 16-hydroperoxide of α-linolenic acid ((16S)-HPOT) to form the α-ketol we recently described, 15-oxo-16-hydroxy-9,12-octadecadienoic acid. Thus, BnAOS is a 13/16-specific AOS. Prior to this study, the ability to efficiently convert (16S)-HPOT was described only in the cucumber CsAOS (CYP74A1) and tomato LeAOS3 (CYP74C3).","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 9","pages":"1716 - 1730"},"PeriodicalIF":2.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098402","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}

引用次数: 0

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-08-29 DOI: 10.1134/S0006297926600985

Marina A. Yakovleva, Alexey A. Kostyukov, Natalya L. Aronshtam, Patimat M. Shilkrot, Sergei A. Borzenok, Vladimir A. Kuzmin, Tatiana B. Feldman, Aleksandr E. Dontsov, Mikhail A. Ostrovsky

{"title":"Age-Related Changes in bis-Retinoids of Lipofuscin Granules in Human Retinal Pigment Epithelium Cells","authors":"Marina A. Yakovleva, Alexey A. Kostyukov, Natalya L. Aronshtam, Patimat M. Shilkrot, Sergei A. Borzenok, Vladimir A. Kuzmin, Tatiana B. Feldman, Aleksandr E. Dontsov, Mikhail A. Ostrovsky","doi":"10.1134/S0006297926600985","DOIUrl":"10.1134/S0006297926600985","url":null,"abstract":"Lipofuscin granules (LGs) in retinal pigment epithelium (RPE) cells contain bis-retinoids and their oxidation and degradation products, rendering them photo- and cytotoxic to intracellular structures. LGs are implicated in the pathogenesis of multiple visual pathologies, including age-related macular degeneration (AMD). They exhibit strong autofluorescence, which has led to the development of fundus autofluorescence (FAF) imaging as a non-invasive diagnostic method in ophthalmology. Spectral analysis of autofluorescence can expand the capabilities of this method, including for preclinical diagnostics, as pathological conditions are often associated with increased proportions of oxidized bis-retinoid derivatives that alter LG autofluorescence parameters. However, limited knowledge of age-dependent changes in LG bis-retinoid composition remains a key limitation. In this study, we combined fluorescence spectroscopy, confocal fluorescence microscopy, and fluorescence lifetime imaging (time-correlated single-photon counting) to demonstrate that, under physiological conditions, aging is accompanied by a progressive increase in the relative abundance of oxidation and degradation products of bis-retinoids in LGs. These findings provide an age-dependent baseline for distinguishing physiological and pathological states, thereby improving the potential of FAF imaging for early (preclinical) diagnosis.","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 8","pages":"1417 - 1431"},"PeriodicalIF":2.1,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838095","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}

引用次数: 0

Effect of Cu2+ on the Nucleoli of Cultured Astrocytes from the Rat Cerebral Cortex Cu2+对培养大鼠大脑皮层星形胶质细胞核仁的影响

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-08-29 DOI: 10.1134/S0006297926601140

Elizaveta E. Genrikhs, Elena V. Stelmashook, Elena A. Smirnova, Sergey A. Golyshev, Alina E. Lapieva, Olga P. Alexandrova, Marina R. Kapkaeva, Nickolay K. Isaev

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Structural and Functional Analysis of the Recombinant Aureobasidium pullulans Cutinase Variants for Efficient Polycaprolactone Degradation 高效降解聚己内酯的重组普鲁兰毛霉角质酶变体的结构和功能分析

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-08-29 DOI: 10.1134/S0006297926601449

Filipp K. Ermilov, Elena V. Eneiskaya, Svetlana A. Panasenko, Elena V. Zhurishkina, Kirill S. Bobrov, Mikhail G. Petukhov, Anna A. Kulminskaya, Irina A. Sizova

{"title":"Structural and Functional Analysis of the Recombinant Aureobasidium pullulans Cutinase Variants for Efficient Polycaprolactone Degradation","authors":"Filipp K. Ermilov, Elena V. Eneiskaya, Svetlana A. Panasenko, Elena V. Zhurishkina, Kirill S. Bobrov, Mikhail G. Petukhov, Anna A. Kulminskaya, Irina A. Sizova","doi":"10.1134/S0006297926601449","DOIUrl":"10.1134/S0006297926601449","url":null,"abstract":"Polycaprolactone (PCL) is a biodegradable polyester widely used in industry, but it degrades slowly in the environment. Enzymatic hydrolysis catalyzed by cutinases represents a promising approach for PCL waste utilization. Through screening, we selected the Aureobasidium pullulans VKM 1116 strain capable of degrading PCL. We amplified the ApCUT1 cutinase gene from the A. pullulans VKM 1116 genomic DNA. Heterologous expression in Komagataella phaffii yielded ~60 mg/L of the target protein. The recombinant enzyme exhibited maximum activity at pH 6.0-6.5 and 30-40°C. Using site-directed mutagenesis, we generated single mutants (Y58W and L186F) and a double mutant (Y58W/L186F). The double mutant demonstrated the highest catalytic efficiency toward the model substrate 4-nitrophenyl 16-methylsulfonyl hexadecanoate (4-NP-(16-MS-C16)), exhibiting a two-fold increase in the hydrolysis rate compared to the wild-type enzyme. During PCL hydrolysis, the Y58W mutant showed the highest activity, providing a 1.8-fold increase in the suspension degradation rate and complete polymer granule degradation at a rate of 1 mg/h per 1 mg of protein. Our molecular modeling suggests that the hydrophobic bridge at the entrance to the active site functions as a “molecular trap.” For the low-molecular-weight substrate (4-NP-(16-MS-C16)), enzymatic activity is limited by the kinetics of the substrate retention step, which is consistent with the maximum catalytic efficiency of the Y58W/L186F mutant with a closing trap. Conversely, activity toward PCL is limited by the initial adsorption stage, for which an open conformation of the free enzyme – as observed in the Y58W variant – is critically important. These results demonstrate the potential of the ApCUT1_Y58W cutinase for developing advanced PCL recycling technologies.","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 8","pages":"1470 - 1479"},"PeriodicalIF":2.1,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838334","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}

引用次数: 0

Dynamics of Aspartate Isomerization and Its Cellular Implications: Evidence for Isoaspartate Formation in ER-Folded Proteins and Stress-Responsive Regulation of PCMT1 天冬氨酸异构化动力学及其细胞意义：内质网折叠蛋白异天冬氨酸形成和PCMT1应激响应调控的证据

IF 2.1 4区生物学

Biochemistry (Moscow) Pub Date : 2026-08-29 DOI: 10.1134/S0006297926600894

Burcu Biterge

{"title":"Dynamics of Aspartate Isomerization and Its Cellular Implications: Evidence for Isoaspartate Formation in ER-Folded Proteins and Stress-Responsive Regulation of PCMT1","authors":"Burcu Biterge","doi":"10.1134/S0006297926600894","DOIUrl":"10.1134/S0006297926600894","url":null,"abstract":"Spontaneous isomerization of aspartate and deamidation of asparagine residues into isoaspartate (isoAsp) constitute major non-enzymatic post-translational modifications that alter protein structure, stability, and turnover. The repair enzyme protein L-isoaspartate O-methyltransferase (PCMT1) catalyzes methylation of isoAsp residues, thereby preventing their accumulation and preserving proteome integrity. Although PCMT1 has been studied extensively in cytoplasm and nucleus, its relationship to endoplasmic reticulum (ER) proteostasis remains poorly understood. Here, we investigated dynamics of aspartate isomerization within the cell, focusing on isoAsp accumulation and the regulation of PCMT1 localization under physiological and stress conditions. Using immunofluorescence, subcellular fractionation, and in vitro methylation assays, we detected isoAsp-modified proteins within the ER-enriched fractions of HeLa cells. We found that ER stress induction enhanced formation of isoAsp-containing proteins, with MG132 treatment producing the highest accumulation. PCMT1 expression increased under both stress conditions, accompanied by distinct subcellular redistribution between the cytoplasmic and nuclear compartments. These observations indicate that ER-folded proteins are susceptible to spontaneous aspartate isomerization, and that PCMT1 activity dynamically responds to proteostatic stress. Our findings provide the first experimental evidence linking isoAsp formation within the ER to PCMT1-mediated protein repair, thereby integrating chemical instability with cellular quality-control pathways. This study establishes a structural and cellular framework for understanding the dynamics of aspartate isomerization in the cell and underscores significance of PCMT1 in maintaining proteostasis under stress conditions.","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"91 8","pages":"1449 - 1459"},"PeriodicalIF":2.1,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838093","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}

引用次数: 0