Biochemistry (Moscow)最新文献

{"title":"CYP74B34 Enzyme from Carrot (Daucus carota) with a Double Hydroperoxide Lyase/Epoxyalcohol Synthase Activity: Identification and Biochemical Properties","authors":"Yana Y. Toporkova,&nbsp;Svetlana S. Gorina,&nbsp;Tatiana M. Iljina,&nbsp;Natalia V. Lantsova,&nbsp;Alexander N. Grechkin","doi":"10.1134/S0006297924080108","DOIUrl":"10.1134/S0006297924080108","url":null,"abstract":"<p>The lipoxygenase cascade in plants is a source of oxylipins (oxidized fatty acid derivatives), which play an important role in regulatory processes and formation of plant response to stress factors. Some of the most common enzymes of the lipoxygenase cascade are 13-specific hydroperoxide lyases (HPLs, also called hemiacetal synthases) of the CYP74B subfamily. In this work, we identified and cloned the <i>CYP74B34</i> gene from carrot (<i>Daucus carota</i> L.) and described the biochemical properties of the corresponding recombinant enzyme. The CYP74B34 enzyme was active towards 9- and 13-hydroperoxides of linoleic (9-HPOD and 13-HPOD, respectively) and α-linolenic (9-HPOT and 13-HPOT, respectively) acids. CYP74B34 specifically converted 9-HPOT and 13-HPOT into aldo acids (HPL products). The transformation of 13-HPOD led to the formation of aldo acids and epoxyalcohols [products of epoxyalcohol synthase (EAS) activity] as major and minor products, respectively. At the same time, conversion of 9-HPOD resulted in the formation of epoxyalcohols as the main products and aldo acids as the minor ones. Therefore, CYP74B34 is the first enzyme with a double HPL/EAS activity described in carrot. The presence of these catalytic activities was confirmed by analysis of the oxylipin profiles for the roots from young seedlings and mature plants. In addition, we substituted amino acid residues in one of the catalytically essential sites of the CYP74B34 and CYP74B33 proteins and investigated the properties of the obtained mutant enzymes.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 8","pages":"1519 - 1530"},"PeriodicalIF":2.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152928","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":"Erratum to: Pharmacological Doses of Thiamine Benefit Patients with the Charcot–Marie–Tooth Neuropathy by Changing Thiamine Diphosphate Levels and Affecting Regulation of Thiamine-Dependent Enzymes","authors":"Artem V. Artiukhov,&nbsp;Olga N. Solovjeva,&nbsp;Natalia V. Balashova,&nbsp;Olga P. Sidorova,&nbsp;Anastasia V. Graf,&nbsp;Victoria I. Bunik","doi":"10.1134/S000629792408011X","DOIUrl":"10.1134/S000629792408011X","url":null,"abstract":"","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 8","pages":"1531 - 1532"},"PeriodicalIF":2.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152932","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":"Epigenetic Phenomenon of Paramutation in Plants and Animals","authors":"Dina A. Kulikova,&nbsp;Alina V. Bespalova,&nbsp;Elena S. Zelentsova,&nbsp;Mikhail B. Evgen’ev,&nbsp;Sergei Yu. Funikov","doi":"10.1134/S0006297924080054","DOIUrl":"10.1134/S0006297924080054","url":null,"abstract":"<p>The phenomenon of paramutation describes the interaction between two alleles, in which one allele initiates inherited epigenetic conversion of another allele without affecting the DNA sequence. Epigenetic transformations due to paramutation are accompanied by the change in DNA and/or histone methylation patterns, affecting gene expression. Studies of paramutation in plants and animals have identified small non-coding RNAs as the main effector molecules required for the initiation of epigenetic changes in gene loci. Due to the fact that small non-coding RNAs can be transmitted across generations, the paramutation effect can be inherited and maintained in a population. In this review, we will systematically analyze examples of paramutation in different living systems described so far, highlighting common and different molecular and genetic aspects of paramutation between organisms, and considering the role of this phenomenon in evolution.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 8","pages":"1429 - 1450"},"PeriodicalIF":2.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152930","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":"RNA Editing by ADAR Adenosine Deaminases in the Cell Models of CAG Repeat Expansion Diseases: Significant Effect of Differentiation from Stem Cells into Brain Organoids in the Absence of Substantial Influence of CAG Repeats on the Level of Editing","authors":"Viacheslav V. Kudriavskii,&nbsp;Anton O. Goncharov,&nbsp;Artem V. Eremeev,&nbsp;Evgenii S. Ruchko,&nbsp;Vladimir A. Veselovsky,&nbsp;Ksenia M. Klimina,&nbsp;Alexandra N. Bogomazova,&nbsp;Maria A. Lagarkova,&nbsp;Sergei A. Moshkovskii,&nbsp;Anna A. Kliuchnikova","doi":"10.1134/S0006297924080078","DOIUrl":"10.1134/S0006297924080078","url":null,"abstract":"<p>Expansion of CAG repeats in certain genes is a known cause of several neurodegenerative diseases, but exact mechanism behind this is not yet fully understood. It is believed that the double-stranded RNA regions formed by CAG repeats could be harmful to the cell. This study aimed to test the hypothesis that these RNA regions might potentially interfere with ADAR RNA editing enzymes, leading to the reduced A-to-I editing of RNA and activation of the interferon response. We studied induced pluripotent stem cells (iPSCs) derived from the patients with Huntington’s disease or ataxia type 17, as well as midbrain organoids developed from these cells. A targeted panel for next-generation sequencing was used to assess editing in the specific RNA regions. Differentiation of iPSCs into brain organoids led to increase in the ADAR2 gene expression and decrease in the expression of protein inhibitors of RNA editing. As a result, there was increase in the editing of specific ADAR2 substrates, which allowed identification of differential substrates of ADAR isoforms. However, comparison of the pathology and control groups did not show differences in the editing levels among the iPSCs. Additionally, brain organoids with 42-46 CAG repeats did not exhibit global changes. On the other hand, brain organoids with the highest number of CAG repeats in the huntingtin gene (76) showed significant decrease in the level of RNA editing of specific transcripts, potentially involving ADAR1. Notably, editing of the long non-coding RNA <i>PWAR5</i> was nearly absent in this sample. It could be stated in conclusion that in most cultures with repeat expansion, the hypothesized effect on RNA editing was not confirmed.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 8","pages":"1474 - 1489"},"PeriodicalIF":2.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152913","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":"Functional Analysis of the Channelrhodopsin Genes from the Green Algae of the White Sea Basin","authors":"Olga V. Karpova,&nbsp;Elizaveta N. Vinogradova,&nbsp;Anastasiya M. Moisenovich,&nbsp;Oksana B. Pustovit,&nbsp;Alla A. Ramonova,&nbsp;Denis V. Abramochkin,&nbsp;Elena S. Lobakova","doi":"10.1134/S0006297924080030","DOIUrl":"10.1134/S0006297924080030","url":null,"abstract":"<p>Optogenetics, the method of light-controlled regulation of cellular processes is based on the use of the channelrhodopsins that directly generate photoinduced currents. Most of the channelrhodopsin genes have been identified in the green microalgae Chlorophyta, and the demand for increasing the number of functionally characterized channelrhodopsins and the diversity of their photochemical parameters keeps growing. We performed the expression analysis of cation channelrhodopsin (CCR) genes in natural isolates of microalgae of the genera <i>Haematococcus</i> and <i>Bracteacoccus</i> from the unique Arctic Circle region. The identified full-length CCR transcript of <i>H. lacustris</i> is the product of alternative splicing and encodes the Hl98CCR2 protein with no photochemical activity. The 5′-partial fragment of the <i>B. aggregatus</i> CCR transcript encodes the Ba34CCR protein containing a conserved TM1-TM7 membrane domain and a short cytosolic fragment. Upon heterologous expression of the TM1-TM7 fragment in CHO-K1 cell culture, light-dependent current generation was observed with the parameters corresponding to those of the CCR. The first discovered functional channelrhodopsin of <i>Bracteacoccus</i> has no close CCR homologues and may be of interest as a candidate for optogenetics.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 8","pages":"1392 - 1401"},"PeriodicalIF":2.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297924080030.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Graphene-Based Materials with the Targeted Action for Cancer Theranostics","authors":"Konstantin N. Semenov,&nbsp;Olga S. Shemchuk,&nbsp;Sergei V. Ageev,&nbsp;Pavel A. Andoskin,&nbsp;Gleb O. Iurev,&nbsp;Igor V. Murin,&nbsp;Pavel K. Kozhukhov,&nbsp;Dmitriy N. Maystrenko,&nbsp;Oleg E. Molchanov,&nbsp;Dilafruz K. Kholmurodova,&nbsp;Jasur A. Rizaev,&nbsp;Vladimir V. Sharoyko","doi":"10.1134/S0006297924080029","DOIUrl":"10.1134/S0006297924080029","url":null,"abstract":"<p>The review summarises the prospects in the application of graphene and graphene-based nanomaterials (GBNs) in nanomedicine, including drug delivery, photothermal and photodynamic therapy, and theranostics in cancer treatment. The application of GBNs in various areas of science and medicine is due to the unique properties of graphene allowing the development of novel ground-breaking biomedical applications. The review describes current approaches to the production of new targeting graphene-based biomedical agents for the chemotherapy, photothermal therapy, and photodynamic therapy of tumors. Analysis of publications and FDA databases showed that despite numerous clinical studies of graphene-based materials conducted worldwide, there is a lack of information on the clinical trials on the use of graphene-based conjugates for the targeted drug delivery and diagnostics. The review will be helpful for researchers working in development of carbon nanostructures, material science, medicinal chemistry, and nanobiomedicine.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 8","pages":"1362 - 1391"},"PeriodicalIF":2.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297924080029.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain-Derived Neurotrophic Factor (BDNF) in the Frontal Cortex Enhances Social Interest in the BTBR Mouse Model of Autism","authors":"Yana P. Kaminskaya,&nbsp;Tatiana V. Ilchibaeva,&nbsp;Alexandra I. Shcherbakova,&nbsp;Elina R. Allayarova,&nbsp;Nina K. Popova,&nbsp;Vladimir S. Naumenko,&nbsp;Anton S. Tsybko","doi":"10.1134/S0006297924080091","DOIUrl":"10.1134/S0006297924080091","url":null,"abstract":"<p>A large body of evidence implies the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of autism spectrum disorders (ASDs). A deficiency of BDNF in the hippocampus and frontal cortex of BTBR mice (a model of autism) has been noted in a number of studies. Earlier, we showed that induction of BDNF overexpression in the hippocampus of BTBR mice reduced anxiety and severity of stereotyped behavior, but did not affect social interest. Here, we induced BDNF overexpression in the frontal cortex neurons of BTBR mice using an adeno-associated viral vector, which resulted in a significant increase in the social interest in the three-chamber social test. At the same time, the stereotypy, exploratory behavior, anxiety-like behavior, and novel object recognition were not affected. Therefore, we have shown for the first time that the presence of BDNF in the frontal cortex is critical for the expression of social interest in BTBR mice, since compensation for its deficiency in this structure eliminated the autism-like deficiencies in the social behavior characteristic for these animals.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 8","pages":"1509 - 1518"},"PeriodicalIF":2.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152927","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":"Computational Assessment of Carotenoids as Keap1-Nrf2 Protein–Protein Interaction Inhibitors: Implications for Antioxidant Strategies","authors":"Alessandro Medoro, Tassadaq Hussain Jafar, Fabio Sallustio, Giovanni Scapagnini, Luciano Saso, Sergio Davinelli","doi":"10.1134/s0006297924100031","DOIUrl":"https://doi.org/10.1134/s0006297924100031","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The Keap1-Nrf2 pathway is an essential system that maintains redox homeostasis and modulates key metabolic processes, including metabolism of amino acids to promote the synthesis of antioxidant enzymes. Inhibitors of the protein-protein interaction (PPI) between Keap1 and Nrf2 have emerged as a promising strategy for developing novel classes of antioxidant agents that selectively activate this pathway without off-target effects. Carotenoids, a large family of lipophilic isoprenoids synthesized by all photosynthetic organisms, are well-known for their antioxidant activities. However, the ability of carotenoids to inhibit the Keap1-Nrf2 PPI through the involvement of specific amino acid residues has not yet been revealed. We utilized molecular docking, molecular dynamic simulations, and pharmacokinetic prediction techniques to investigate the potential of eight oxygenated carotenoids, known as xanthophylls, to inhibit Keap1. Among the compounds investigated, fucoxanthin and astaxanthin established multiple hydrogen-bonding and hydrophobic interactions within the Kelch domain of Keap1, showing remarkable binding affinities. Furthermore, fucoxanthin and astaxanthin displayed the ability to form a stable complex with Keap1 and fit into the binding pocket of its Kelch domain. These analyses led to the identification of critical amino acid residues in the binding pocket of Keap1 which are involved in the interaction with carotenoid xanthophylls. Our analyses further revealed that fucoxanthin and astaxanthin demonstrate a favorable safety profile and possess pharmacokinetic properties consistent with acceptable drug-like characteristics. These findings lay the preliminary foundation for developing a novel class of Keap1-Nrf2 PPI inhibitors with potential applications against oxidative stress-related diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"1 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185888","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":"Cardiac Myosin and Thin Filament as Targets for Lead and Cadmium Divalent Cations","authors":"Oksana P. Gerzen,&nbsp;Iulia K. Potoskueva,&nbsp;Alena E. Tzybina,&nbsp;Tatiana A. Myachina,&nbsp;Larisa V. Nikitina","doi":"10.1134/S0006297924070095","DOIUrl":"10.1134/S0006297924070095","url":null,"abstract":"<p>Lead and cadmium are heavy metals widely distributed in the environment and contribute significantly to cardiovascular morbidity and mortality. Using Leadmium Green dye, we have shown that lead and cadmium enter cardiomyocytes, distributing throughout the cell. Using an <i>in vitro</i> motility assay, we have shown that sliding velocity of actin and native thin filaments over myosin decreases with increasing concentrations of Pb²⁺ and Cd²⁺. Significantly lower concentrations of Pb²⁺ and Cd²⁺ (0.6 mM) were required to stop sliding of thin filaments over myosin compared to the stopping actin sliding over the same myosin (1.1-1.6 mM). Lower concentration of Cd²⁺ (1.1 mM) needed to stop actin sliding over myosin compared to the Pb²⁺+Cd²⁺ combination (1.3 mM) and lead alone (1.6 mM). There were no differences found in the effects of lead and cadmium cations on relative force developed by myosin heads or number of actin filaments bound to myosin. Sliding velocity of actin over myosin in the left atrium, right and left ventricles changed equally when exposed to the same dose of the same metal. Thus, we have demonstrated for the first time that Pb²⁺ and Cd²⁺ can directly affect myosin and thin filament function, with Cd²⁺ exerting a more toxic influence on myosin function compared to Pb²⁺.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 7","pages":"1273 - 1282"},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103089","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":"Dermal Fibroblast Cell Line from a Patient with the Huntington’s Disease as a Promising Model for Studying Disease Pathogenesis: Production and Characterization","authors":"Nina Kraskovskaya,&nbsp;Anna Koltsova,&nbsp;Polina Parfenova,&nbsp;Alla Shatrova,&nbsp;Natalya Yartseva,&nbsp;Vladimir Nazarov,&nbsp;Ekaterina Devyatkina,&nbsp;Mikhail Khotin,&nbsp;Natalia Mikhailova","doi":"10.1134/S000629792407006X","DOIUrl":"10.1134/S000629792407006X","url":null,"abstract":"<p>Huntington’s disease (HD) is an incurable hereditary disease caused by expansion of the CAG repeats in the <i>HTT</i> gene encoding the mutant huntingtin protein (mHTT). Despite numerous studies in cellular and animal models, the mechanisms underlying the biological role of mHTT and its toxicity to striatal neurons have not yet been established and no effective therapy for HD patients has been developed so far. We produced and characterized a new line of dermal fibroblasts (HDDF, Huntington’s disease dermal fibroblasts) from a patient with a confirmed HD diagnosis. We also studied the growth characteristics of HDDF cells, stained them for canonical markers, karyotyped these cells, and investigated their phenotype. HDDF cells was successfully reprogrammed into induced striatal neurons via transdifferentiation. The new fibroblast line can be used as a cell model to study the biological role of mHTT and manifestations of HD pathogenesis in both fibroblasts and induced neuronal cells obtained from them by reprogramming techniques.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 7","pages":"1239 - 1250"},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103091","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}