Biochemistry (Moscow)最新文献

{"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":null,"pages":null},"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":"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":null,"pages":null},"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":"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":null,"pages":null},"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":"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}

{"title":"Mechanism of PARP1 Elongation Reaction Revealed by Molecular Modeling","authors":"Sergey V. Pushkarev,&nbsp;Evgeny M. Kirilin,&nbsp;Vytas K. Švedas,&nbsp;Dmitry K. Nilov","doi":"10.1134/S0006297924070046","DOIUrl":"10.1134/S0006297924070046","url":null,"abstract":"<p>Poly(ADP-ribose) polymerase 1 (PARP1) plays a major role in the DNA damage repair and transcriptional regulation, and is targeted by a number of clinical inhibitors. Despite this, catalytic mechanism of PARP1 remains largely underexplored because of the complex substrate/product structure. Using molecular modeling and metadynamics simulations we have described in detail elongation of poly(ADP-ribose) chain in the PARP1 active site. It was shown that elongation reaction proceeds via the S_N1-like mechanism involving formation of the intermediate furanosyl oxocarbenium ion. Intriguingly, nucleophilic 2′_A-OH group of the acceptor substrate can be activated by the general base Glu988 not directly but through the proton relay system including the adjacent 3′_A-OH group.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297924070046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103097","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":"Content of Primary and Secondary Carotenoids in the Cells of Cryotolerant Microalgae Chloromonas reticulata","authors":"Olga V. Dymova,&nbsp;Vitaliy S. Parshukov,&nbsp;Irina V. Novakovskaya,&nbsp;Elena N. Patova","doi":"10.1134/S0006297924070071","DOIUrl":"10.1134/S0006297924070071","url":null,"abstract":"<p>Snow (cryotolerant) algae often form red (pink) spots in mountain ecosystems on snowfields around the world, but little is known about their physiology and chemical composition. Content and composition of pigments in the cells of the cryotolerant green microalgae <i>Chloromonas reticulata</i> have been studied. Analysis of carotenoids content in the green (vegetative) cells grown under laboratory conditions and in the red resting cells collected from the snow surface in the Subpolar Urals was carried out. Carotenoids such as neoxanthin, violaxanthin, anteraxanthin, zeaxanthin, lutein, and β-carotene were detected. Among the carotenoids, the ketocarotenoid astaxanthin with high biological activity was also found. It was established that cultivation of the algae at low positive temperature (6°C) and moderate illumination (250 μmol quanta/(m²⋅s) contributed to accumulation of all identified carotenoids, including extraplastidic astaxanthin. In addition to the pigments, fatty acids accumulated in the algae cells. The data obtained allow us to consider the studied microalgae as a potentially promising species for production of carotenoids.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103090","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":"Differences in the Effect of Beta-Hydroxybutyrate on the Mitochondrial Biogenesis, Oxidative Stress and Inflammation Markers in Tissues from Young and Old Rats","authors":"Veronika V. Nesterova,&nbsp;Polina I. Babenkova,&nbsp;Anna A. Brezgunova,&nbsp;Natalia A. Samoylova,&nbsp;Irina S. Sadovnikova,&nbsp;Dmitry S. Semenovich,&nbsp;Nadezda V. Andrianova,&nbsp;Artem P. Gureev,&nbsp;Egor Y. Plotnikov","doi":"10.1134/S0006297924070149","DOIUrl":"10.1134/S0006297924070149","url":null,"abstract":"<p>One of the therapeutic approaches to age-related diseases is modulation of body cell metabolism through certain diets or their pharmacological mimetics. The ketogenic diet significantly affects cell energy metabolism and functioning of mitochondria, which has been actively studied in various age-related pathologies. Here, we investigated the effect of the ketogenic diet mimetic beta-hydroxybutyrate (BHB) on the expression of genes regulating mitochondrial biogenesis (<i>Ppargc1a</i>, <i>Nrf1</i>, <i>Tfam)</i>, quality control (<i>Sqstm1</i>), functioning of the antioxidant system (<i>Nfe2l2</i>, <i>Gpx1</i>, <i>Gpx3</i>, <i>Srxn1</i>, <i>Txnrd2</i>, <i>Slc6a9</i>, <i>Slc7a11</i>), and inflammatory response (<i>Il1b</i>, <i>Tnf</i>, <i>Ptgs2</i>, <i>Gfap</i>) in the brain, lungs, heart, liver, kidneys, and muscles of young and old rats. We also analyzed mitochondrial DNA (mtDNA) copy number, accumulation of mtDNA damage, and levels of oxidative stress based on the concentration of reduced glutathione and thiobarbituric acid-reactive substances (TBARS). In some organs, aging disrupted mitochondrial biogenesis and functioning of cell antioxidant system, which was accompanied by the increased oxidative stress and inflammation. Administration of BHB for 2 weeks had different effects on the organs of young and old rats. In particular, BHB upregulated expression of genes coding for proteins associated with the mitochondrial biogenesis and antioxidant system, especially in the liver and muscles of young (but not old) rats. At the same time, BHB contributed to the reduction of TBARS in the kidneys of old rats. Therefore, our study has shown that administration of ketone bodies significantly affected gene expression in organs, especially in young rats, by promoting mitochondrial biogenesis, improving the functioning of the antioxidant defense system, and partially reducing the level of oxidative stress. However, these changes were much less pronounced in old animals.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103092","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":"Femtosecond Dynamics of the Excited Primary Electron Donor in Reaction Centers of the Purple Bacterium Rhodobacter sphaeroides","authors":"Anton M. Khristin,&nbsp;Tatyana Yu. Fufina,&nbsp;Ravil A. Khatypov","doi":"10.1134/S0006297924070125","DOIUrl":"10.1134/S0006297924070125","url":null,"abstract":"<p>Femtosecond transient absorption spectroscopy was used to study the dynamics of the excited primary electron donor in the reaction centers of the purple bacterium <i>Rhodobacter sphaeroides</i>. Using global analysis and the interval method, we found a correlation between the vibrational coherence damping of the excited primary electron donor and the lifetime of the charge-separated state P⁺B_A⁻, indicating the reversibility of electron transfer to the primary electron acceptor, the B_A molecule. In the reaction centers, the signs of superposition of two electronic states of P were found for a delay time of less than 200 fs. It is suggested that the admixture value of the charge transfer state P_A⁺P_B⁻ with the excited primary electron donor P* is about 24%. The results obtained are discussed in terms of the two-step electron transfer mechanism.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103095","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}