Biochemistry (Moscow)最新文献

{"title":"Placental Transport of Amino Acids in Rats with Methionine-Induced Hyperhomocysteinemia.","authors":"Yulia P Milyutina, Gleb O Kerkeshko, Dmitrii S Vasilev, Irina V Zalozniaia, Sergey K Bochkovskii, Natalia L Tumanova, Anastasiia D Shcherbitskaia, Anastasiia V Mikhel, Gulrukhsor H Tolibova, Alexander V Arutjunyan","doi":"10.1134/S0006297924100055","DOIUrl":"https://doi.org/10.1134/S0006297924100055","url":null,"abstract":"<p><p>Maternal hyperhomocysteinemia (HHcy) is a risk factor for intrauterine growth restriction presumably caused by a decrease in the placental transport of nutrients. We investigated the effect of experimental HHcy induced by daily methionine administration to pregnant rats on the free amino acid levels in the maternal and fetal blood, as well as on morphological and biochemical parameters associated with the amino acid transport through the placenta. HHcy caused an increase in the levels of most free amino acids in the maternal blood on gestational day 20, while the levels of some amino acids in the fetal blood were decreased. In rats with HHcy, the maternal sinusoids in the placental labyrinth were narrowed, which was accompanied by aggregation of red blood cells. We also observed an increase in the neutral amino acid transporters (LAT1, SNAT2) protein levels and activation of 4E-BP1, a downstream effector of mTORC1 complex, in the labyrinth zone. Maternal HHcy affected the placental barrier permeability, as evidenced by intensification of the mother-to-fetus transfer of Evans Blue dye. The imbalance in the free amino acid levels in the maternal and fetal blood in HHcy may be due to the competition of homocysteine with other amino acids for common transporters, as well as a decrease in the area of exchange zone between maternal and fetal circulations in the placental labyrinth. Upregulation of the neutral amino acid transporter expression in the labyrinth zone may be a compensatory response to an insufficient intrauterine amino acid supply and fetal growth restriction.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1711-1726"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611936","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":"Glioblastoma Sensitization to Therapeutic Effects by Glutamine Deprivation Depends on Cellular Phenotype and Metabolism.","authors":"Alina A Isakova, Irina N Druzhkova, Artem M Mozherov, Diana V Mazur, Nadezhda V Antipova, Kirill S Krasnov, Roman S Fadeev, Marine E Gasparian, Anne V Yagolovich","doi":"10.1134/S0006297924100079","DOIUrl":"https://doi.org/10.1134/S0006297924100079","url":null,"abstract":"<p><p>Glutamine plays an important role in tumor metabolism. It is known that the core region of solid tumors is deprived of glutamine, which affects tumor growth and spread. Here we investigated the effect of glutamine deprivation on cellular metabolism and sensitivity of human glioblastoma cells U87MG and T98G to drugs of various origin: alkylating cytostatic agent temozolomide; cytokine TRAIL DR5-B - agonist of the DR5 receptor; and GMX1778 - a targeted inhibitor of the enzyme nicotinamide phosphoribosyltransferase (NAMPT), limiting NAD biosynthesis. Bioinformatics analysis of the cell transcriptomes showed that U87MG cells have a more differentiated phenotype than T98G, and also differ in the expression profile of the genes associated with glutamine metabolism. Upon glutamine deprivation, growth rate of the U87MG and T98G cells decreased. Analysis of cellular metabolism by FLIM microscopy of NADH as well as assessment of lactate content in the medium showed that glutamine deprivation shifted metabolic status of the U87MG cells towards glycolysis. This was accompanied by the increase in expression of the stemness marker CD133, which collectively could indicate de-differentiation of these cells. At the same time, we observed increase in both expression of the DR5 receptor and sensitivity of the U87MG cells to DR5-B. On the contrary, glutamine deprivation of T98G cells induced metabolic shift towards oxidative phosphorylation, decrease in the DR5 expression and resistance to DR5-B. The effects of NAMPT inhibition also differed between the two cell lines and were opposite to the effects of DR5-B: upon glutamine deprivation, U87MG cells acquired resistance, while T98G cells were sensitized to GMX1778. Thus, phenotypic and metabolic differences between the two human glioblastoma cell lines caused divergent metabolic changes and contrasting responses to different targeted drugs during glutamine deprivation. These data should be considered when developing treatment strategies for glioblastoma via drug-mediated deprivation of amino acids, as well as when exploring novel therapeutic targets.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1744-1758"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611927","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":"ω-Amidase and Its Substrate α-Ketoglutaramate (the α-Keto Acid Analogue of Glutamine) as Biomarkers in Health and Disease.","authors":"Arthur J L Cooper, Travis T Denton","doi":"10.1134/S000629792410002X","DOIUrl":"https://doi.org/10.1134/S000629792410002X","url":null,"abstract":"<p><p>A large literature exists on the biochemistry, chemistry, metabolism, and clinical importance of the α-keto acid analogues of many amino acids. However, although glutamine is the most abundant amino acid in human tissues, and transamination of glutamine to its α-keto acid analogue (α-ketoglutaramate; KGM) was described more than seventy years ago, little information is available on the biological importance of KGM. Herein, we summarize the metabolic importance of KGM as an intermediate in the glutamine transaminase - ω-amidase (GTωA) pathway for the conversion of glutamine to anaplerotic α-ketoglutarate. We describe some properties of KGM, notably its occurrence as a lactam (2-hydroxy-5-oxoproline; 99.7% at pH 7.2), and its presence in normal tissues and body fluids. We note that the concentration of KGM is elevated in the cerebrospinal fluid of liver disease patients and that the urinary KGM/creatinine ratio is elevated in patients with an inborn error of the urea cycle and in patients with citrin deficiency. Recently, of the 607 urinary metabolites measured in a kidney disease study, KGM was noted to be one of five metabolites that was most significantly associated with uromodulin (a potential biomarker for tubular functional mass). Finally, we note that KGM is an intermediate in the breakdown of nicotine in certain organisms and is an important factor in nitrogen homeostasis in some microorganisms and plants. In conclusion, we suggest that biochemists and clinicians should consider KGM as (i) a key intermediate in nitrogen metabolism in all branches of life, and (ii) a biomarker, along with ω-amidase, in several diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1660-1680"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611939","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":"Combined Administration of Metformin and Amprolium to Rats Affects Metabolism of Free Amino Acids in the Brain, Altering Behavior, and Heart Rate.","authors":"Anastasia V Graf, Artem V Artiukhov, Olga N Solovjeva, Alexander L Ksenofontov, Victoria I Bunik","doi":"10.1134/S0006297924100043","DOIUrl":"https://doi.org/10.1134/S0006297924100043","url":null,"abstract":"<p><p>The risk of developing diabetes and cardiometabolic disorders is associated with increased levels of alpha-aminoadipic acid and disturbances in the metabolism of branched-chain amino acids. The side effects of the widely used antidiabetic drug metformin include impaired degradation of branched-chain amino acids and inhibition of intracellular thiamin transport. These effects may be interconnected, as thiamine deficiency impairs the functioning of thiamine diphosphate (ThDP)-dependent dehydrogenases of 2-oxo acids involved in amino acids degradation, while diabetes is often associated with perturbed thiamine status. In this work, we investigate the action of metformin in rats with impaired thiamine availability. The reduction in the thiamine influx is induced by simultaneous administration of the thiamine transporters inhibitors metformin and amprolium. After 24 days of combined metformin/amprolium administration, no significant changes in the total brain levels of ThDP or activities of ThDP-dependent enzymes of central metabolism are observed, but the affinities of transketolase and 2-oxoglutarate dehydrogenase to ThDP increase. The treatment also significantly elevates the brain levels of free amino acids and ammonia, reduces the antioxidant defense, and alters the sympathetic/parasympathetic regulation, which is evident from changes in the ECG and behavioral parameters. Strong positive correlations between brain ThDP levels and contents of ammonia, glutathione disulfide, alpha-aminoadipate, glycine, citrulline, and ethanolamine are observed in the metformin/amprolium-treated rats, but not in the control animals. Analysis of the obtained data points to a switch in the metabolic impact of ThDP from the antioxidant and nitrogen-sparing in the control rats to the pro-oxidant and hyperammonemic in the metformin/amprolium-treated rats. As a result, metformin administration along with the amprolium-reduced thiamine supply significantly perturb the metabolism of amino acids in the rat brain, altering behavioral and ECG parameters.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1692-1710"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611916","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":"Accumulation of Li⁺ Ions Triggers Changes in <i>FOS</i>, <i>JUN</i>, <i>EGR1</i>, and <i>MYC</i> Transcription in the LiCl-Treated Human Umbilical Vein Endothelial Cells (HUVEC).","authors":"Olga E Kvitko, Dmitrii A Fedorov, Svetlana V Sidorenko, Olga D Lopina, Elizaveta A Klimanova","doi":"10.1134/S0006297924100146","DOIUrl":"https://doi.org/10.1134/S0006297924100146","url":null,"abstract":"<p><p>Changes in intracellular concentrations of Na⁺ and K⁺ are shown to alter gene expression. Another monovalent cation, Li⁺, is well known as a medicine for treatment of psychiatric disorders, but mechanism of its action is obscure. Thus, it is important to evaluate the effect of Li⁺ on gene expression in endothelial cells. Here we studied influence of the increased intracellular Na⁺ or Li⁺ concentrations on transcription of Na⁺_i/K⁺_i-sensitive genes. Treatment of the human endothelial cells (HUVEC) with LiCl for 1.5 h resulted in accumulation of Li⁺ in the cells. This was followed by increase in the <i>FOS</i> and <i>EGR1</i> mRNAs levels and decrease in the <i>JUN</i> and <i>MYC</i> mRNA levels. Treatment of HUVEC with the Na⁺-ionophore monensin led to accumulation of Na⁺ and loss of K⁺ ions. However, monensin had no significant effect on gene expression. Incubation of HUVEC with elevated extracellular NaCl concentration increased intracellular K⁺ concentration and transcription of the <i>ATF3</i> gene, while transcription of the <i>JUN</i> gene decreased. These results indicate that Na⁺ and Li⁺ ions have different effects on the gene expression profile in the cells that is likely associated with the fact that they affect differently the intracellular monovalent cations ratio.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1844-1850"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611877","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":"Comparative Study of Spectral and Functional Properties of Wild Type and Double Mutant H(L173)L/I(L177)H Reaction Centers of the Purple Bacterium <i>Cereibacter sphaeroides</i>.","authors":"Tatiana Yu Fufina, Alexey A Zabelin, Ravil A Khatypov, Anton M Khristin, Anatoly Ya Shkuropatov, Lyudmila G Vasilieva","doi":"10.1134/S0006297924100109","DOIUrl":"https://doi.org/10.1134/S0006297924100109","url":null,"abstract":"<p><p>Previously, we found that in the reaction center (RC) of the purple bacterium <i>Cereibacter sphaeroides</i>, formation of heterodimeric primary electron donor (P) caused by the substitution of His-L173 by Leu, was compensated by the second mutation Ile-L177 - His. Significant changes in the spectral properties, pigment composition, and redox potential of P observed in the H(L173)L RC, are restored to the corresponding characteristics of the native RC in the RC H(L173)L/I(L177)H, with the difference that the energy of the long-wavelength Q_Y optical transition of P increases significantly (by ~75 meV). In this work, it was shown using light-induced difference FTIR spectroscopy that the homodimeric structure of P is preserved in the RC with double mutation with partially altered electronic properties: electronic coupling in the radical-cation of the P⁺ dimer is weakened and localization of the positive charge on one of its halves is increased. Results of the study of the triple mutant RC, H(L173)L/I(L177)H/F(M197)H, are consistent with the assumption that the observed changes in the P⁺ electronic structure, as well as considerable blue shift of the Q_Y P absorption band in the RC H(L173)L/I(L177)H, are associated with modification of the spatial position and/or geometry of P. Using femtosecond transient absorption spectroscopy, it was shown that the mutant H(L173)L/I(L177)H RC retains a sequence of reactions P* → P⁺B_A^- → P⁺H_A^- → P⁺Q_A^- with electron transfer rates and the quantum yield of the final state P⁺Q_A^- close to those observed in the wild-type RC (P* is the singlet-excited state of P; B_A, H_A, and Q_A are molecules of bacteriochlorophyll, bacteriopheophytin, and ubiquinone in the active A-branch of cofactors, respectively). The obtained results, together with the previously published data for the RC with symmetrical double mutation H(M202)L/I(M206)H, demonstrate that by introducing additional point amino acid substitutions, photochemical activity of the isolated RC from <i>C. sphaeroides</i> could be maintained at a high level even in the absence of important structural elements - axial histidine ligands of the primary electron donor P.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1789-1802"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611919","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":"Kinetics of Electron Transfer between Redox Cofactors in Photosystem I Measured by High-Frequency EPR Spectroscopy.","authors":"Andrey A Sukhanov, Georgy E Milanovsky, Liya A Vitukhnovskaya, Mahir D Mamedov, Kev M Salikhov, Alexey Yu Semenov","doi":"10.1134/S0006297924100158","DOIUrl":"https://doi.org/10.1134/S0006297924100158","url":null,"abstract":"<p><p>The kinetics of the primary electron donor P₇₀₀⁺ and the quinone acceptor A₁^- redox transitions were simultaneously studied for the first time in the time range of 200 μs-10 ms using high-frequency pulse Q-band EPR spectroscopy at cryogenic temperatures in various complexes of photosystem I (PSI) from the cyanobacterium <i>Synechocystis sp.</i> PCC 6803. In the A₁-core PSI complexes that lack 4Fe4S clusters, the kinetics of the A₁^- and P₇₀₀⁺ signals disappearance at 100 K were similar and had a characteristic time of τ ≈ 500 μs, caused by charge recombination in the P₇₀₀⁺A_1A^- ion-radical pair in the <i>A</i> branch of redox cofactors. The kinetics of the backward electron transfer from A_1B^- to P₇₀₀⁺ in the <i>B</i> branch of redox cofactors with τ &lt; 100 μs could not be resolved due to time limitations of the method. In the native PSI complexes with a full set of redox cofactors and in the F_X-core complexes, containing the 4Fe4S cluster F_X, the kinetics of the A₁^- signal was significantly faster than that of the P₇₀₀⁺ signal. The disappearance of the A₁^- signal had a characteristic time of 280-350 μs; it was suggested that, in addition to the backward electron transfer from A_1A^- to P₇₀₀⁺ with τ ≈ 500 μs, its kinetics also includes the forward electron transfer from A_1A^- to the 4Fe4S cluster F_X, which had slowed down to 150-200 μs. In the kinetics of P₇₀₀⁺ reduction, it was possible to distinguish components caused by the backward electron transfer from A₁^- (τ ≈ 500 μs) and from 4Fe4S clusters (τ = 1 ms for the F_X-core and τ &gt; 5 ms for native complexes). These results are in qualitative agreement with the data on the kinetics of P₇₀₀⁺ reduction obtained previously using pulse absorption spectrometry at cryogenic temperatures.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1851-1862"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611932","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":"Gene Expression and Pathway Activation Biomarkers of Breast Cancer Sensitivity to Taxanes.","authors":"Daniil Luppov, Maxim Sorokin, Marianna Zolotovskaya, Marina Sekacheva, Maria Suntsova, Galina Zakharova, Anton Buzdin","doi":"10.1134/S0006297924100110","DOIUrl":"https://doi.org/10.1134/S0006297924100110","url":null,"abstract":"<p><p>Taxanes are one of the most widely used classes of breast cancer (BC) therapeutics. Despite the long history of clinical usage, the molecular mechanisms of their action and cancer resistance are still not fully understood. Here we aimed to identify gene expression and molecular pathway activation biomarkers of BC sensitivity to taxane drugs paclitaxel and docetaxel. We used to our knowledge the biggest collection of clinically annotated publicly available literature BC gene expression data (12 datasets, <i>n</i> = 1250) and the experimental clinical BC cohort (<i>n</i> = 12). Seven literature datasets were used for biomarker discovery (<i>n</i> = 914), and the remaining five literature plus one experimental datasets (<i>n</i> = 336) - for the validation. We totally found 34 genes and 29 molecular pathways which could strongly discriminate good and poor responders to taxane treatments. The biomarker genes and pathways were associated with molecular processes related to formation of mitotic spindle and centromeres, and with the spindle assembly mitotic checkpoint. Furthermore, we created gene expression and pathway activation signatures predicting BC response to taxanes. These signatures were tested on the validation BC cohort and demonstrated strong biomarker potential reflected by mean AUC values of 0.76 and 0.77, respectively, which outperforms previously reported analogs. Taken together, these findings can deepen our understanding of mechanism of action of taxanes and potentially improve personalization of treatment in BC.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1803-1822"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611925","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":"Astaxanthin Reduces H₂O₂- and Doxorubicin-Induced Cardiotoxicity in H9c2 Cardiomyocyte Cells.","authors":"Roman R Krestinin, Margarita I Kobyakova, Yuliya L Baburina, Linda D Sotnikova, Olga V Krestinina","doi":"10.1134/S0006297924100122","DOIUrl":"https://doi.org/10.1134/S0006297924100122","url":null,"abstract":"<p><p>Cardiovascular diseases are among the most challenging problems in clinical practice. Astaxanthin (AST) is a keto-carotenoid (xanthophyll) mainly of marine origin, which is able to penetrate the cell membrane, localize in mitochondria, and prevent mitochondrial dysfunction. In this study effect of astaxanthin on the death of H9c2 cardiomyocytes caused by the cytotoxic effect of hydrogen peroxide (H₂O₂) and doxorubicin (DOX) was examined. Using methods of spectrophotometry, spectrofluorimetry, and Western blotting analysis, it was shown that treatment of the cells with AST contributed to the increase in the number of H9c2 cells resistant to H₂O₂ and doxorubicin, while maintaining the value of their mitochondrial transmembrane potential, reducing intracellular production of reactive oxygen species, and increasing intracellular content of the mitophagy markers PINK1, Parkin, and prohibitin 2. The obtained results suggest that the use of AST could be a highly effective way to prevent and treat cardiovascular diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1823-1833"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611901","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":"Analysis of Expression of the <i>GRIPAP1</i>, <i>DLG4</i>, <i>KIF1B</i>, <i>NGFRAP1</i>, and <i>NRF1</i> Genes in Peripheral Blood of the Patients with Parkinson's Disease in the Early Clinical Stages.","authors":"Maria V Lukashevich, Margarita M Rudenok, Ekaterina I Semenova, Suzanna A Partevian, Alexey V Karabanov, Elena Yu Fedotova, Sergey N Illarioshkin, Petr A Slominsky, Maria I Shadrina, Anelya Kh Alieva","doi":"10.1134/S0006297924100092","DOIUrl":"https://doi.org/10.1134/S0006297924100092","url":null,"abstract":"<p><p>Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. An important feature of the disease is its long latent period, which necessitates search for prognostic biomarkers. One method of identifying biomarkers of PD is to study changes in gene expression in peripheral blood of the patients in early stages of the disease and have not been treated. In this study, we analyzed relative mRNA levels of the genes <i>GRIPAP1</i>, <i>DLG4</i>, <i>KIF1B</i>, <i>NGFRAP1</i>, and <i>NRF1</i>, which are associated with neurotransmitter transport, apoptosis, and mitochondrial dysfunction, in the peripheral blood of PD patients using reverse transcription and real-time PCR with TaqMan probes. The results of this study suggest that the <i>GRIPAP1</i> and <i>DLG4</i> genes could be considered as potential biomarkers for the early clinical stages of Parkinson's disease. The data obtained may indicate that <i>NGFRAP1</i> is involved in pathogenesis of both PD and other neurodegenerative diseases. Furthermore, in the early clinical stages of the disease we studied, the <i>KIF1B</i> and <i>NRF1</i> genes were found not to be involved in PD pathogenesis at the expression level.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 10","pages":"1779-1788"},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611898","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}