Biochimie最新文献_第2页

Site-directed mutagenesis of nattokinase: Unveiling structure-function relationship for enhanced functionality. 纳豆激酶的定点突变：揭示结构-功能关系以增强功能

Biochimie Pub Date : 2025-02-01 Epub Date: 2024-09-26 DOI: 10.1016/j.biochi.2024.09.014

Ankush Jain, Pradeep Kumar Anand, Jagdeep Kaur

{"title":"Site-directed mutagenesis of nattokinase: Unveiling structure-function relationship for enhanced functionality.","authors":"Ankush Jain, Pradeep Kumar Anand, Jagdeep Kaur","doi":"10.1016/j.biochi.2024.09.014","DOIUrl":"10.1016/j.biochi.2024.09.014","url":null,"abstract":"Site-directed mutagenesis was employed to investigate the structure-function relationship of nattokinase (NK) and its effect on the enzymatic activity, thermostability, pH tolerance, and fibrinolytic properties of NK. Specific mutations (T270S, V271I, E262D, and A259T) were introduced within the nk gene, targeting regions predicted to be involved in substrate binding. The NK(E262D) mutant exhibited a significant increase in enzymatic activity (2-fold) and catalytic efficiency (2.2-fold) as assessed by N-Succinyl-Ala-Ala-Pro-Phe p-nitroanilide (Suc-AAPF-pNA) hydrolysis, compared to the wild type. In silico analysis supported these findings, demonstrating lower binding energy for the NK(E262D) mutant, suggesting stronger fibrin affinity. Thermostability assays revealed that NK(E262D) and NK(A259T) displayed exceptional stability, retaining enzyme activity at 60 °C. All mutants exhibited a broader pH tolerance range (pH 5.0-10.0) compared to the wild-type NK. The fibrinolytic activity assay revealed that the E262D mutant possessed the highest fibrinolytic activity (2414 U/mg), surpassing the wild-type. This study reported an NK variant with improved enzymatic activity, thermostability, and fibrinolytic properties.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of extremolytes ectoine and hydroxyectoine on the heat-induced protein aggregation: The case of growth hormone. 极性溶解物埃克托因和羟基埃克托因对热诱导蛋白质聚集的影响：以生长激素为例

Biochimie Pub Date : 2025-02-01 Epub Date: 2024-10-09 DOI: 10.1016/j.biochi.2024.10.006

Rūta Gruškienė, Jolanta Sereikaitė

{"title":"The effect of extremolytes ectoine and hydroxyectoine on the heat-induced protein aggregation: The case of growth hormone.","authors":"Rūta Gruškienė, Jolanta Sereikaitė","doi":"10.1016/j.biochi.2024.10.006","DOIUrl":"10.1016/j.biochi.2024.10.006","url":null,"abstract":"The extremolytes ectoine and hydroxyectoine are osmolytes found in extremophilic microorganisms. They are stabilisers of proteins and other macromolecules, including DNA and lipids. The aim of the study was to investigate the effect of the additives on the heat-induced aggregation of mink growth hormone as a model protein. The first-order rate constants of protein aggregation were determined at 60 °C depending on the additive concentration and pH of the solution. The onset temperature of aggregation was also recorded using a circular dichroism spectropolarimeter. The study showed that the effect of the additives depended on the pH of the solution. The first-order rate constants of aggregation were lower when the protein molecule had a negative charge. The effect also depended on the structure of the extremolyte itself. When the protein molecule was positively charged, hydroxyectoine destabilised the mink growth hormone molecule and promoted the aggregation. The different effects of the additives were determined by the different interactions with the protein molecules, as shown by circular dichroism measurements and previously by fluorescence spectroscopy. Therefore, when using ectoine or hydroxyectoine for protein formulation, the effect of the additive should be carefully analysed for each protein individually.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":"42-48"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neutrophils and purinergic signaling: partners in the crime against Leishmania parasites?

Biochimie Pub Date : 2025-01-22 DOI: 10.1016/j.biochi.2025.01.004

Mariana M Chaves

引用次数: 0

Structure and Function Analysis of Microcystin Transport Protein MlrD.

Biochimie Pub Date : 2025-01-20 DOI: 10.1016/j.biochi.2025.01.005

Jiaqi Li, Huanhuan Sun, Huasheng Wang, Fengqiu Zhou, Wenyu Wu, Dan Chen, Zhengning Zhou, Hai Yan

{"title":"Structure and Function Analysis of Microcystin Transport Protein MlrD.","authors":"Jiaqi Li, Huanhuan Sun, Huasheng Wang, Fengqiu Zhou, Wenyu Wu, Dan Chen, Zhengning Zhou, Hai Yan","doi":"10.1016/j.biochi.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.biochi.2025.01.005","url":null,"abstract":"Microorganisms play a crucial role in the degradation of microcystins (MCs), with most MC-degrading bacteria utilizing the mlr gene cluster (mlrABCD) mechanism. While previous studies have advanced our understanding of the structure, function, and degradation mechanisms of MlrA, MlrB, and MlrC, research on MlrD remains limited. Consequently, the molecular structure and specific catalytic processes of MlrD are still unclear. This study investigates MlrD from Sphingopyxis sp. USTB-05, utilizing bioinformatics tools for analysis and prediction, conducting homology analysis, and constructing the molecular structure of MlrD. Bioinformatics analysis suggests that MlrD is an alkaline, hydrophobic protein with good thermal stability and is likely located in the cell membrane as a membrane protein without a signal peptide. Homology analysis indicates that MlrD belongs to the PTR2 protein family and contains a PTR2 domain. Phylogenetic analysis reveals that MlrD follows both vertical and horizontal genetic transfer patterns during evolution. Homology modeling demonstrates that the three-dimensional structure of MlrD is primarily composed of 12 α-helices, with conserved residues between the N-terminal and C-terminal domains forming a large reaction cavity. This research broadens current knowledge of MC biodegradation and offers a promising foundation for future studies.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Macrolactin A Is an Inhibitor of Protein Biosynthesis in Bacteria. 大泌乳素A是细菌中蛋白质生物合成的抑制剂。

Biochimie Pub Date : 2025-01-16 DOI: 10.1016/j.biochi.2025.01.003

Alexey S Vasilchenko, Dmitry A Lukyanov, Diana S Dilbaryan, Konstantin S Usachev, Darya V Poshvina, Amir Taldaev, Arina A Nikandrova, Arina N Imamutdinova, Natalia S Garaeva, Aydar G Bikmullin, Evelina A Klochkova, Alexander L Rusanov, Daniil D Romashin, Natalia G Luzgina, Ilya A Osterman, Petr V Sergiev, Anastasia V Teslya

{"title":"Macrolactin A Is an Inhibitor of Protein Biosynthesis in Bacteria.","authors":"Alexey S Vasilchenko, Dmitry A Lukyanov, Diana S Dilbaryan, Konstantin S Usachev, Darya V Poshvina, Amir Taldaev, Arina A Nikandrova, Arina N Imamutdinova, Natalia S Garaeva, Aydar G Bikmullin, Evelina A Klochkova, Alexander L Rusanov, Daniil D Romashin, Natalia G Luzgina, Ilya A Osterman, Petr V Sergiev, Anastasia V Teslya","doi":"10.1016/j.biochi.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.biochi.2025.01.003","url":null,"abstract":"Macrolactin A (McA) is a secondary metabolite produced by Bacillus species. It has been known for its antimicrobial properties since the late 1980s, although the exact mechanism of its antibacterial activity remains unknown. In this study, we have found that McA is an inhibitor of protein synthesis in bacteria. Our conclusion is based on the results obtained by in vivo and in vitro bioreporter systems. We demonstrated that the inhibitory activity of McA is independent of bacterial species. However, the concentration of McA required to inhibit protein synthesis in the E. coli cell-free translational model was found to be 50 times lower than the concentration required in the S. aureus cell-free translational model. To investigate the mechanism of McA's inhibitory activity, we conducted a toe-printing assay, sequenced and annotated the genomes of McA-resistant Bacillus pumilus McAR and its parental strain. The results showed that McA inhibits the initial step of the elongation phase of protein synthesis. We identified single and multiple nucleotide polymorphisms in the gene encoding the translation elongation factor Tu (EF-Tu). Molecular modeling showed that the McA molecule can form non-covalent bonds with amino acids at the interface of domains 1 and 2 of EF-Tu. A cross-resistance assay was conducted using kirromycin on B. pumilus McAR. The results confirmed the assumption that McA has a mode of action similar to that of other elfamycin-like antibiotics (targeting EF-Tu). Overall, our study addresses a significant gap in our understanding of the mechanism of action of McA, a representative member of the macrolide family.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Redesigning methionine γ-lyase for improved stability and catalytic activity in the β-elimination reaction for the synthesis of thiosulfinates. 重新设计蛋氨酸γ-裂解酶，提高β-消除反应合成硫代亚硫酸盐的稳定性和催化活性。

Biochimie Pub Date : 2025-01-15 DOI: 10.1016/j.biochi.2025.01.002

Vitalia Kulikova, Natalya Anufrieva, Elena Morozova, Kseniya Levshina, Svetlana Revtovich, Pavel Solyev

{"title":"Redesigning methionine γ-lyase for improved stability and catalytic activity in the β-elimination reaction for the synthesis of thiosulfinates.","authors":"Vitalia Kulikova, Natalya Anufrieva, Elena Morozova, Kseniya Levshina, Svetlana Revtovich, Pavel Solyev","doi":"10.1016/j.biochi.2025.01.002","DOIUrl":"10.1016/j.biochi.2025.01.002","url":null,"abstract":"Pyridoxal 5'-phosphate (PLP)-dependent enzymes are involved in many cellular processes and possess unequalled catalytic versatility. Rational design through site-directed mutagenesis is a powerful strategy for creating tailor-made enzymes for a wide range of biocatalytic applications. PLP-dependent methionine γ-lyase (MGL), which degrades sulfur-containing amino acids, is an encouraging enzyme for many therapeutic purposes - from combating bacterial resistant strains and fungi to antitumor activity. A two-component biosystem MGL/S-alk(en)yl-l-cysteine sulfoxide (an uncommon substrate for this enzyme) produces antimicrobial thiosulfinates during the β-elimination reaction. SH-groups of the enzyme are modified by the products of this reaction, which leads to the inactivation of the enzyme. Successful and efficient rational stabilization of MGL from Clostridium novyi can be achieved using site-directed mutagenesis. We have managed to obtain an improved version of the enzyme better than the natural one regarding the β-elimination reaction. Cys118, Cys184 and Cys273 of MGL from Clostridium novyi were substituted by His and two Ala, respectively. The resulting Cys-del variant had 2-3-fold improved kcat/Km value for conventional β-eliminating substrates and up to 10-fold increase in catalytic efficiency with S-substituted-l-cysteine sulfoxides compared to the wild-type MGL. The Cys-del MGL remained active under the thiosulfinates, which are products of β-elimination reaction of S-alk(en)yl-l-cysteine sulfoxides. Moreover, Cys-del variant proved to be more stable during shelf storage. Thus, we have created an effective enzyme component of the biocatalytic system that is capable of generating antimicrobial drugs - thiosulfinates.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interaction of small heat shock proteins with BAG3. 小热休克蛋白与bag3的相互作用。

Biochimie Pub Date : 2025-01-13 DOI: 10.1016/j.biochi.2025.01.001

Maria A Zamotina, Lydia K Muranova, Arthur I Zabolotskii, Nikolai B Gusev

{"title":"Interaction of small heat shock proteins with BAG3.","authors":"Maria A Zamotina, Lydia K Muranova, Arthur I Zabolotskii, Nikolai B Gusev","doi":"10.1016/j.biochi.2025.01.001","DOIUrl":"10.1016/j.biochi.2025.01.001","url":null,"abstract":"BAG3 is a universal adapter protein involved in various cellular processes, including the regulation of apoptosis, chaperone-assisted selective autophagy, and heat shock protein function. The interaction between small heat shock proteins (sHsps) and their α-crystallin domains (Acds) with full-length BAG3 protein and its IPV domain was analyzed using size-exclusion chromatography, native gel electrophoresis, and chemical cross-linking. HspB7 and the 3D mutant of HspB1 (which mimics phosphorylation) showed no interaction, HspB6 weakly interacted, and HspB8 strongly interacted with full-length BAG3. In contrast to the full-length sHsps, their α-crystallin domains (AcdB1, AcdB5, and AcdB6) were able to interact with BAG3, with AcdB8 again being the strongest interactor. Among all the full-length sHsps analyzed, only HspB8 bound to the IPV domain of BAG3. AcdB1, AcdB5, AcdB6, and AcdB8 interacted with the IPV domain of BAG3, with AcdB8 displaying the highest binding efficiency. The stoichiometry of crosslinked complexes formed by HspB8 (or its Acd) and the IPV domain of BAG3 was 2:1, whereas for the other sHsps and their Acds, it was 1:1. These findings suggest that while the IPV domain of BAG3 and the Acds of sHsps play an important role in binding, other structural regions significantly contribute to this interaction. The unique binding efficiency between BAG3 and HspB8 may be attributed to the intrinsic disorder and simple oligomeric structure of HspB8.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elucidating on the Quaternary Structure of Viper Venom Phospholipase A₂ Enzymes in Aqueous Solution. 蛇毒磷脂酶A2在水溶液中的四级元结构研究。

Biochimie Pub Date : 2025-01-10 DOI: 10.1016/j.biochi.2024.12.015

Joana R da Silva, Maria João Ramos, Pedro A Fernandes

{"title":"Elucidating on the Quaternary Structure of Viper Venom Phospholipase A2 Enzymes in Aqueous Solution.","authors":"Joana R da Silva, Maria João Ramos, Pedro A Fernandes","doi":"10.1016/j.biochi.2024.12.015","DOIUrl":"https://doi.org/10.1016/j.biochi.2024.12.015","url":null,"abstract":"This study focuses on the quaternary structure of the viper-secreted phospholipase A2 (PLA2), a central toxin in viper envenomation. PLA2 enzymes catalyse the hydrolysis of the sn-2 ester bond of membrane phospholipids. Small-molecule inhibitors that act as snakebite antidotes, such as varespladib, are currently in clinical trials. These inhibitors likely bind to the enzyme in the aqueous cytosol prior to membrane-binding. Thus, understanding its controversial solution structure is key for drug design. Crystal structures of PLA2 in the PDB show at least four different dimeric conformations, the most well-known being \"extended\" and \"compact\". This variability among enzymes with >50% sequence identity raises questions about their transferability to aqueous solution. Therefore, we performed extensive molecular dynamics (MD) simulations of several PLA2 enzymes in water to determine their quaternary structure under physiological conditions. The MD simulations strongly indicate that PLA2 enzymes adopt a \"semi-compact\" conformation in cytosol, a hybrid between extended and compact conformations. To our knowledge, this is the first study that determines the most favorable dimeric conformation of PLA2 enzymes in solution, providing a basis for advancements in snakebite envenoming treatment. Recognizing snakebite envenoming as a neglected tropical disease has driven the search for efficient, affordable alternatives to the current antivenoms. Therefore, understanding the main drug targets within snake venom is crucial to this achievement.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Luminescence-based complementation assay to assess target engagement and cell permeability of glycolate oxidase (HAO1) inhibitors. 基于荧光的互补测定法，用于评估乙醇酸氧化酶（HAO1）抑制剂的靶参与性和细胞渗透性。

Biochimie Pub Date : 2025-01-01 Epub Date: 2024-08-14 DOI: 10.1016/j.biochi.2024.08.011

Sabrina R Mackinnon, Tryfon Zarganes-Tzitzikas, Cassandra J Adams, Paul E Brennan, Wyatt W Yue

{"title":"Luminescence-based complementation assay to assess target engagement and cell permeability of glycolate oxidase (HAO1) inhibitors.","authors":"Sabrina R Mackinnon, Tryfon Zarganes-Tzitzikas, Cassandra J Adams, Paul E Brennan, Wyatt W Yue","doi":"10.1016/j.biochi.2024.08.011","DOIUrl":"10.1016/j.biochi.2024.08.011","url":null,"abstract":"Glycolate oxidase (HAO1) catalyses the synthesis of glyoxylate, a common metabolic intermediate that causes renal failure if accumulated. HAO1 inhibition is an emerging treatment for primary hyperoxaluria, a rare disorder of glyoxylate metabolism. Here we report the first cell-based measurement of inhibitor uptake and engagement with HAO1, by adapting the cellular thermal shift assay (CETSA) based on Nano luciferase complementation and luminescence readout. By profiling the interaction between HAO1 and four well-characterised inhibitors in intact and lysed HEK293T cells, we showed that our CETSA method differentiates between low-permeability/high-engagement and high-permeability/low-engagement ligands and is able to rank HAO1 inhibitors in line with both recombinant protein methods and previously reported indirect cellular assays. Our methodology addresses the unmet need for a robust, sensitive, and scalable cellular assay to guide HAO1 inhibitor development and, in broader terms, can be rapidly adapted for other targets to simultaneously monitor compound affinity and cellular permeability.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":"71-81"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enzymatic activity of HIV-1 protease defines migration of tumor cells in vitro and enhances their metastatic activity in vivo. hiv-1 蛋白酶的酶活性决定了肿瘤细胞在体外的迁移并增强其在体内的转移活性。

Biochimie Pub Date : 2025-01-01 Epub Date: 2024-08-14 DOI: 10.1016/j.biochi.2024.08.009

M Isaguliants, A Zhitkevich, S Petkov, T Gorodnicheva, D Mezale, I Fridrihsone, Y Kuzmenko, D Kostyushev, A Kostyusheva, I Gordeychuk, E Bayurova

{"title":"Enzymatic activity of HIV-1 protease defines migration of tumor cells in vitro and enhances their metastatic activity in vivo.","authors":"M Isaguliants, A Zhitkevich, S Petkov, T Gorodnicheva, D Mezale, I Fridrihsone, Y Kuzmenko, D Kostyushev, A Kostyusheva, I Gordeychuk, E Bayurova","doi":"10.1016/j.biochi.2024.08.009","DOIUrl":"10.1016/j.biochi.2024.08.009","url":null,"abstract":"Overexpression of aspartic proteases, as cathepsin D, is an independent marker of poor prognosis in breast cancer, correlated with the incidence of clinical metastasis. We aimed to find if HIV-1 aspartic protease (PR) can play a similar role. Murine adenocarcinoma 4T1luc2 cells were transduced with lentivirus encoding inactivated drug-resistant PR, generating subclones PR20.1 and PR20.2. Subclones were assessed for production of reactive oxygen species (ROS), expression of epithelial-mesenchymal transition (EMT) factors, and in vitro migratory activity in the presence or absence of antioxidant N-acetyl cysteine and protease inhibitors. Tumorigenic activity was evaluated by implanting cells into BALB/c mice and following tumor growth by calipering and bioluminescence imaging in vivo, and metastases, by organ imaging ex vivo. Both subclones expressed PR mRNA, and PR20.2, also the protein detected by Western blotting. PR did not induce production of ROS, and had no direct effect on cell migration rate, however, treatment with inhibitors of drug-resistant PR suppressed the migratory activity of both subclones. Furthermore, expression of N-cadherin and Vimentin in PR20.2 cells and their migration were enhanced by antioxidant treatment. Sensitivity of in vitro migration to protease inhibitors and to antioxidant, known to restore PR activity, related the effects to the enzymatic activity of PR. In vivo, PR20.2 cells demonstrated higher tumorigenic and metastatic activity than PR20.1 or parental cells. Thus, HIV-1 protease expressed in breast cancer cells determines their migration in vitro and metastatic activity in vivo. This effect may aggravate clinical course of cancers in people living with HIV-1.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":"32-43"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0