Biochimie最新文献_第10页

Does hypersialylation compensate the functional Alpha1-AntiTrypsin (A1AT) deficiency in all critically ill patients? 高ialylation 是否能弥补所有重症患者的功能性 Alpha1-AntiTrypsin (A1AT) 缺乏症？

Biochimie Pub Date : 2024-11-17 DOI: 10.1016/j.biochi.2024.11.008

Malika Balduyck, Sarah Afif, Brigitte Onraed, Mercédes Jourdain, Saad Nseir, Pascal Pigny, Farid Zerimech

{"title":"Does hypersialylation compensate the functional Alpha1-AntiTrypsin (A1AT) deficiency in all critically ill patients?","authors":"Malika Balduyck, Sarah Afif, Brigitte Onraed, Mercédes Jourdain, Saad Nseir, Pascal Pigny, Farid Zerimech","doi":"10.1016/j.biochi.2024.11.008","DOIUrl":"10.1016/j.biochi.2024.11.008","url":null,"abstract":"Alpha-1 antitrypsin (A1AT) is the major circulating serine protease inhibitor. Hypersialylated glycoforms (HSG) are produced to boost A1AT anti-inflammatory and anti-protease properties. Their occurrence and prognostic impact outside severe COVID-19 or community-acquired pneumonia are unknown. Our aim was to clarify the occurrence of A1AT functional deficiency and HSG in patients admitted into intensive care unit (ICU) for any cause. A1AT and elastase inhibitory capacity (EIC) were measured in serum. Functional A1AT deficiency was defined by a measured EIC/calculated EIC Ratio ≤0.85. HSG were identified by isoelectrofocusing and quantified by gel densitometry. A total of 248 serum samples was analyzed, 173 from COVID-19 and 75 from non COVID-19 patients. A functional A1AT deficiency occurred 3-fold more frequently in non-COVID-19 than in COVID-19 patients: 18.7 % vs 6.9 % and was not associated with more frequent S/Z deficient alleles. Functional deficiency was also more frequent in deceased than alive patients in COVID-19 group. M0 and M1 HSG of A1AT occurred in around half of patients but the relative proportion of M1 significantly increased in deceased vs alive patients only in the non-COVID-19 group explaining the absence of worsening of the functional deficiency. In conclusion, our study shows that a functional A1AT deficiency is more frequently observed in patients admitted to the ICU for a cause unrelated to COVID-19, as well as in those with an unfavorable evolution. Among the latter, only those admitted for non-COVID-19 tried to compensate the functional deficiency by increasing the proportion of M1 HSG of A1AT.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670090","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

Regulation of adipokine and batokine secretion by dietary flavonoids, as a prospective therapeutic approach for obesity and its metabolic complications. 通过膳食类黄酮调节脂肪因子和蝙蝠素的分泌，作为肥胖症及其代谢并发症的一种前瞻性治疗方法。

Biochimie Pub Date : 2024-11-15 DOI: 10.1016/j.biochi.2024.11.007

Khanyisani Ziqubu, Sithandiwe E Mazibuko-Mbeje, Phiwayinkosi V Dludla

{"title":"Regulation of adipokine and batokine secretion by dietary flavonoids, as a prospective therapeutic approach for obesity and its metabolic complications.","authors":"Khanyisani Ziqubu, Sithandiwe E Mazibuko-Mbeje, Phiwayinkosi V Dludla","doi":"10.1016/j.biochi.2024.11.007","DOIUrl":"10.1016/j.biochi.2024.11.007","url":null,"abstract":"Traditionally recognised as the energy reservoir and main site of adaptive thermogenesis, white and brown adipose tissues are complex endocrine organs regulating systemic energy metabolism via the secretion of bioactive molecules, termed \"adipokines\" and \"batokines\", respectively. Due to its significant role in regulating whole-body energy metabolism and other physiological processes, adipose tissue has been increasingly explored as a feasible therapeutic target for obesity. Flavonoids are one of the most significant plant polyphenolic compounds holding a great potential as therapeutic agents for combating obesity. However, understanding their mechanisms of action remains largely insufficient to formulate therapeutic theories. This review critically discusses scientific evidence highlighting the role of flavonoids in ameliorating obesity-related metabolic complications, including adipose tissue dysfunction, inflammation, insulin resistance, hepatic steatosis, and cardiovascular comorbidities in part by modulating the release of adipokines and batokines. Further discussion advocates for the use of therapeutics targeting these bioactive molecules as a potential avenue for developing effective treatment for obesity and its adverse metabolic diseases such as type 2 diabetes.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649991","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 l-Arginine pathway may act as a mediator in the association between impaired one-carbon metabolism and hypertension. 左旋精氨酸途径可能是一碳代谢受损与高血压之间关系的介质。

Biochimie Pub Date : 2024-11-15 DOI: 10.1016/j.biochi.2024.11.006

Carla Ramos-Rodríguez, Alejandra Rojas-Gomez, Luis A Santos-Calderón, Santiago Ceruelo, Lídia Ríos, Per M Ueland, Joan D Fernandez-Ballart, Albert Salas-Huetos, Michelle M Murphy

{"title":"The l-Arginine pathway may act as a mediator in the association between impaired one-carbon metabolism and hypertension.","authors":"Carla Ramos-Rodríguez, Alejandra Rojas-Gomez, Luis A Santos-Calderón, Santiago Ceruelo, Lídia Ríos, Per M Ueland, Joan D Fernandez-Ballart, Albert Salas-Huetos, Michelle M Murphy","doi":"10.1016/j.biochi.2024.11.006","DOIUrl":"10.1016/j.biochi.2024.11.006","url":null,"abstract":"Elevated fasting plasma total homocysteine (tHcy) and the methylenetetrahydrofolate reductase C677T polymorphism (rs1801133) have been associated with hypertension. Whether the l-Arginine pathway is involved, is unclear. We aimed to investigate whether the association between tHcy, the rs1801133 polymorphism and hypertension involves the l-Arginine pathway. THcy, plasma folate and cobalamin, erythrocyte glutathionine reductase activation coefficient, rs1801133 genotype, plasma l-Arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were determined in a cross-sectional study of 788 adults (aged 18 to 75), randomly selected from 2 town population registers. Participants participated in a medical checkup and provided a fasting blood sample. Associations between tHcy, rs1801133 genotype and l-Arginine pathway metabolites were assessed by multiple linear regression analysis and whether the tHcy and rs1801133 genotype are associated with hypertension via the l-Arginine pathway was investigated using mediation analysis. tHcy was positively associated with ADMA (B = 0.003; SE = 0.001; P < 0.001) and SDMA (B = 0.007; SE = 0.002; P < 0.001) and negatively associated with the l-Arginine/ADMA (B = -1.140; SE = 0.451; P < 0.05) and ADMA/SDMA (B = -0.006; SE = 0.003; P < 0.05) ratios. The MTHFR 677 CT vs CC genotype was negatively associated with ADMA (B = -0.013; SE = 0.007; P < 0.05) and with SDMA (B = -0.029; SE = 0.013; P < 0.05) in participants under 50 years. Each standard deviation increase (37.6) in the l-Arginine/ADMA ratio was associated with reduced hypertension risk (OR [95%CI], 0.6 [0.5, 0.8]). Mediation analysis showed that tHcy and ADMA were mediators in the association between the rs1801133 TT vs CC genotypes and hypertension. Our results support the l-Arginine pathway as a mediator in the association of impaired One-Carbon metabolism and hypertension.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645307","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

A novel regulatory motif at the hinge dimer interface of the MksB mediates dimerization and DNA binding activity. MksB 铰链二聚体界面上的一个新调节基团介导二聚化和 DNA 结合活性

Biochimie Pub Date : 2024-11-14 DOI: 10.1016/j.biochi.2024.11.005

Pratibha Kumari, Vinayak Hegde, Anant Bakshi, M Suguna, M Dharma Prasad, B S Gnanesh Kumar, Dandamudi Usharani, Kunal Sharan, Ravi Kumar

{"title":"A novel regulatory motif at the hinge dimer interface of the MksB mediates dimerization and DNA binding activity.","authors":"Pratibha Kumari, Vinayak Hegde, Anant Bakshi, M Suguna, M Dharma Prasad, B S Gnanesh Kumar, Dandamudi Usharani, Kunal Sharan, Ravi Kumar","doi":"10.1016/j.biochi.2024.11.005","DOIUrl":"10.1016/j.biochi.2024.11.005","url":null,"abstract":"The Structural Maintenance of Chromosome (SMC) protein is essential for various cellular processes, including chromosome organization, DNA repair, and genome stability. MksB, an alternative SMC protein present in prokaryotes, comprises a hinge dimerization domain and an ABC ATPase head domain linked by a coiled-coil arm. While hinge dimerization in bacterial and eukaryotic SMCs is attributed to conserved glycines, our study unveils the critical role of a novel KDDR motif located at a loop near the hinge dimer interface in Mycobacterium smegmatis MksB (MsMksB). We demonstrate the regulatory role of this motif in MsMksB dimerization and DNA binding activity. The K600D mutation in the KDDR motif induces MsMksB dimer-to-monomer conversion, highlighting the significance of this motif in MsMksB dimerization. Mass spectrometry-based mapping of the DNA binding site revealed the lysine's involvement in protein-DNA interaction. Monomers of the hinge domain lose DNA binding activity, and MsMksB single-arm mutants exhibit reduced DNA binding and ATPase activity, underscoring the importance of hinge-mediated dimerization in MsMksB function. Notably, the R603D mutant retains dimerization but shows compromised ATPase and DNA binding activities. Mutants with defective ATPase activity exhibit impaired DNA condensation in vivo. These findings provide novel regulatory insight into the mechanism of MksB dimerization and DNA binding, uncovering the fundamental processes of chromosome condensation and segregation.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645305","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 role of the gut microbial metabolism of sterols and bile acids in human health. 肠道微生物代谢固醇和胆汁酸对人体健康的作用。

Biochimie Pub Date : 2024-11-13 DOI: 10.1016/j.biochi.2024.11.003

Jiahui Tang, Wenwu Xu, Yangfan Yu, Shengxiang Yin, Bang-Ce Ye, Yunyan Zhou

引用次数: 0

Targeting mono- and dual-species biofilms of Staphylococcus aureus and Pseudomonas aeruginosa by the recombinant anticoagulant enzyme PAPC from micromycete Aspergillus ochraceus. 从微霉菌赭曲霉中提取的重组抗凝血酶 PAPC 针对金黄色葡萄球菌和铜绿假单胞菌的单种和双种生物膜。

Biochimie Pub Date : 2024-11-12 DOI: 10.1016/j.biochi.2024.11.002

Aya Rafea Nasr, Sergei K Komarevtsev, Diana R Baidamshina, Ayan B Ryskulova, Dmitriy A Makarov, Vasiliy N Stepanenko, Elena Yu Trizna, Anna S Gorshkova, Alexander A Osmolovskiy, Konstantin A Miroshnikov, Airat R Kayumov

{"title":"Targeting mono- and dual-species biofilms of Staphylococcus aureus and Pseudomonas aeruginosa by the recombinant anticoagulant enzyme PAPC from micromycete Aspergillus ochraceus.","authors":"Aya Rafea Nasr, Sergei K Komarevtsev, Diana R Baidamshina, Ayan B Ryskulova, Dmitriy A Makarov, Vasiliy N Stepanenko, Elena Yu Trizna, Anna S Gorshkova, Alexander A Osmolovskiy, Konstantin A Miroshnikov, Airat R Kayumov","doi":"10.1016/j.biochi.2024.11.002","DOIUrl":"10.1016/j.biochi.2024.11.002","url":null,"abstract":"Microbial biofilms have recently emerged as a critical target for treating bacterial infections due to their crucial role in developing antibiotic resistance. The wide-spectrum activity of proteolytic enzymes makes them particularly suitable for disrupting biofilms formed by diverse bacterial species, including dual-species biofilms. In this study, we propose the Protease-Activator of Protein C (PAPC) of human blood plasma, an enzyme produced by the micromycete Aspergillus ochraceus, as a novel tool to degrade the protein scaffold of mono- or dual-species biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa. The recombinant PAPC was successfully refolded after expression in E. coli BL21 (DE3) and demonstrated activity 100-fold higher compared to the native enzyme purified from the A. ochraceus culture liquid. The enzyme significantly destroyed mono- and dual-species biofilms formed by S. aureus and P. aeruginosa. In addition, PAPC significantly enhanced the antimicrobial treatment efficacy in both mono- and dual-species biofilms: in the presence of PAPC at 100 μg/ml, the effective concentration of the ciprofloxacin and ceftriaxone was reduced at least four-fold. Thus, the enzyme represents a reasonable solution to the complications resulting from biofilm formation and antibiotic resistance, especially wound and medical devices infections.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634342","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

Mechanical and structural features of three AcSp proteins underlie the diverse material properties of aciniform silks of Neoscona spiders. 三种 AcSp 蛋白的机械和结构特征是 Neoscona 蜘蛛纤丝不同材料特性的基础。

Biochimie Pub Date : 2024-10-31 DOI: 10.1016/j.biochi.2024.10.017

Zheng Peng, Rui Wen

{"title":"Mechanical and structural features of three AcSp proteins underlie the diverse material properties of aciniform silks of Neoscona spiders.","authors":"Zheng Peng, Rui Wen","doi":"10.1016/j.biochi.2024.10.017","DOIUrl":"10.1016/j.biochi.2024.10.017","url":null,"abstract":"Spider silks are desirable multicomponent biomaterials characterized by great tensile strength, extensibility, and biocompatibility. Of all spider silk types, aciniform silk has highest toughness due to its combination of high tensile strength and elsticity. Here, we identify three major spidroin components (AcSp1A, AcSp1B, and AcSp2) from aciniform silk of orbweb weaving spider, Neoscona scylloides, and present their full-length coding gene sequences. Comparative sequence and expression level analysis show that AcSp1B has highest expression level and higher serine content than other two AcSp proteins, while the AcSp2 shows very low mRNA level. Furthermore, three recombinant minimalist AcSp proteins are produced and could be induced to form fibers by shear forces in a physiological buffer. The manual-drawn AcSp1B fiber shows strongest tensile strength among three AcSp fibers because of its higher β-sheet formed by abundant serine content. We also compare mechanical properties of aciniform silks between two Neoscona species (N. theisi and N. scylloides) and found that aciniform silks from N. theisi exhibit higher tensile strength than those of N. scylloides, which may result from altering expression levels of two AcSp1 proteins. Collectively, our results provide insights into the mechanical features of each component in aciniform silk from N. scylloides and reveal the molecular mechanism of diverse material properties of aciniform silk among species.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565167","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 pro-inflammatory responses of innate immune cells to Leishmania RNA virus 2-infected L. major support the survival and proliferation of the parasites. 先天性免疫细胞对感染利什曼病 RNA 病毒 2 的大叶利什曼病的促炎反应支持寄生虫的生存和增殖。

Biochimie Pub Date : 2024-10-23 DOI: 10.1016/j.biochi.2024.10.015

Asal Katebi, Matineh Nouri, Ava Behrouzi, Soheila Ajdary, Farhad Riazi-Rad

{"title":"The pro-inflammatory responses of innate immune cells to Leishmania RNA virus 2-infected L. major support the survival and proliferation of the parasites.","authors":"Asal Katebi, Matineh Nouri, Ava Behrouzi, Soheila Ajdary, Farhad Riazi-Rad","doi":"10.1016/j.biochi.2024.10.015","DOIUrl":"10.1016/j.biochi.2024.10.015","url":null,"abstract":"Infection of Leishmania by Leishmania RNA virus (LRV) has been proposed as a pathogenic factor that induces pro-inflammatory responses through the TLR3/TLR4 signaling pathway. We investigated the effect of L. major infection by LRV2 on innate immune cell responses (human neutrophil (HL-60) and macrophage (THP-1) cell lines). The expression levels of pro- and anti-inflammatory cytokine and chemokine genes as well as genes involved in the amino acid metabolism of arginine were then investigated by RT-qPCR. Moreover, the expression of TLR genes and their downstream signaling pathways were compared in THP-1 cells infected with the two isolates. Apoptosis was also evaluated in infected THP-1 and HL-60 cells using the PI/Annexin V flow cytometry assay. In both cell lines, the expression of pro-inflammatory cytokines increased in response to LRV2+ L. major (Lm+), and the expression of chemokines shifted toward macrophage recruitment. In contrast to LRV2- L. major (Lm-), Lm + infected THP-1 cells acquired the M2-like phenotype. The presence of LRV2 increased the gene expression of TLRs and their signaling pathways, especially TLR3 and TLR4, which was proportional to the increase in pro-inflammatory cytokines. In addition, Lm + increased the expression of IL-10 and IFN-β, which contribute to the survival and growth of the parasite in the phagolysosome. Altogether, our results showed that Lm + could stimulate pro-inflammatory responses that promote parasite replication and stabilization in the host.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514569","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

Robust approach for production of the human oncology target Aurora kinase B in complex with its binding partner INCENP. 生产人类肿瘤靶标极光激酶 b 与其结合伙伴 incenp 复合物的稳健方法。

Biochimie Pub Date : 2024-10-18 DOI: 10.1016/j.biochi.2024.10.011

Jonna Mattsson, Per Rogne, Maréne Landström, Magnus Wolf-Watz

{"title":"Robust approach for production of the human oncology target Aurora kinase B in complex with its binding partner INCENP.","authors":"Jonna Mattsson, Per Rogne, Maréne Landström, Magnus Wolf-Watz","doi":"10.1016/j.biochi.2024.10.011","DOIUrl":"10.1016/j.biochi.2024.10.011","url":null,"abstract":"Protein kinases are key players in many eukaryotic signal transduction cascades and are as a result often linked to human disease. In humans, the mitotic protein kinase family of Aurora kinases consist of three members: Aurora A, B and C. All three members are involved in cell division with proposed implications in various human cancers. The human Aurora kinase B has in particular proven challenging to study with structural biology approaches, and this is mainly due to difficulties in producing the large quantities of active enzyme required for such studies. Here, we present a novel and E. coli-based production system that allows for production of milligram quantities of well-folded and active human Aurora B in complex with its binding partner INCENP. The complex is produced as a continuous polypeptide chain and the resulting fusion protein is cleaved with TEV protease to generate a stable and native heterodimer of the Aurora B:INCENP complex. The activity, stability and degree of phosphorylation of the protein complex was quantified by using a coupled ATPase assay, 31P NMR spectroscopy and mass spectrometry. The developed production system enables isotope labeling and we here report the first 1H-15N-HSQC of the human Aurora B:INCENP complex. Our developed production strategy paves the way for future structural and functional studies of Aurora B and can as such assist the development of novel anticancer drugs targeting this important mitotic protein kinase.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482922","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

In vitro and in vivo evidence of the antineoplastic activity of quercetin against endothelial cells transformed by Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. 槲皮素对由卡波西肉瘤相关疱疹病毒 G 蛋白偶联受体转化的内皮细胞具有抗肿瘤活性的体外和体内证据。

Biochimie Pub Date : 2024-10-05 DOI: 10.1016/j.biochi.2024.10.004

Gabriel Principe, Virginia Lezcano, Silvina Tiburzi, Alicia B Miravalles, Betina N García, Fernanda Gumilar, Verónica González-Pardo

{"title":"In vitro and in vivo evidence of the antineoplastic activity of quercetin against endothelial cells transformed by Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor.","authors":"Gabriel Principe, Virginia Lezcano, Silvina Tiburzi, Alicia B Miravalles, Betina N García, Fernanda Gumilar, Verónica González-Pardo","doi":"10.1016/j.biochi.2024.10.004","DOIUrl":"10.1016/j.biochi.2024.10.004","url":null,"abstract":"Quercetin (QUE) is a natural flavonoid with well-known anticancer capabilities, although its effect on viral-induced cancers is less studied. Kaposi's sarcoma (KS) is a viral cancer caused by the human herpesvirus-8, which, during its lytic phase, expresses a constitutively activated viral G protein-coupled receptor (vGPCR) able to induce oncogenic modifications that lead to tumor development. The aim of this work was to investigate the potential effect of QUE on in vitro and in vivo models of Kaposi's sarcoma, developed by transforming endothelial cells with the vGPCR of Kaposi's sarcoma-associated herpesvirus. Initially, the antiproliferative effect of QUE was determined in endothelial cells stably expressing the vGPCR (vGPCR cells), with an IC50 of 30 μM. Additionally, QUE provoked a decrease in vGPCR cell viability, interfered with the cell cycle progression, and induced apoptosis, as revealed by annexin V/PI analysis and caspase-3 activity. The presence of apoptotic bodies and disorganized actin filaments was observed by SEM and phalloidin staining. Furthermore, tumors from vGPCR cells were induced in nude mice, which were treated with QUE (50 or 100 mg/kg/d) resulting in retarded tumor progression and reduced tumor weight. Notably, neither kidney nor liver damage was observed, as indicated by biochemical parameters in serum. In conclusion, this study suggests for the first time that QUE exhibits antineoplastic activity in both in vitro and in vivo models of KS, marking a starting point for further investigations and protocols for therapeutic purpose.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382735","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