Purinergic Signalling最新文献

{"title":"Editorial-Translation of purinergic drugs into therapeutic use.","authors":"Charles Kennedy","doi":"10.1007/s11302-025-10077-8","DOIUrl":"10.1007/s11302-025-10077-8","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"193"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosmarinic acid modulates purinergic signaling and induces apoptosis in melanoma cells.","authors":"Gilnei B da Silva, Daiane Manica, Paula Dallagnol, Rafael A Narzetti, Filomena Marafon, Alana P da Silva, Letícia de S Matias, Joana V Cassol, Marcelo Moreno, Aniela P Kempka, Margarete D Bagatini","doi":"10.1007/s11302-024-10040-z","DOIUrl":"10.1007/s11302-024-10040-z","url":null,"abstract":"<p><p>Cancer cases have increased worldwide. Cutaneous melanoma (CM), a highly metastatic skin cancer, largely contributes to global statistical cancer death data. Research has shown that rosmarinic acid (RA) is a promising phenolic compound with antineoplastic properties. Thus, we investigated the effects of RA on apoptosis-inducing in melanoma cells, purinergic signaling modulation, and cytokine levels. We treated SK-MEL-28 cells for 24 h with different concentrations of RA and assessed the apoptosis, CD39, CD73, and A2A expression, and cytokine levels. We found RA-induced apoptosis in melanoma cells. Regarding the purinergic system, we verified that RA downregulated the expression of CD73 and A2A, specially at high concentrations of treatment. Additionally, RA increased IL-6, IL-4, IL-10, IFN-γ, and TNF-α levels. Our in vitro results confirm RA's potential to be used to induce melanoma cell apoptosis, having CD73 and A2A as targets when reversion of immune suppression is desired. Further studies in animal models and clinical trials focusing on RA's modulation of purinergic signaling in melanoma are required.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"353-363"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring novel dilazep derivatives as hENT1 inhibitors and potentially covalent molecular tools.","authors":"Majlen A Dilweg, Marina Gorostiola González, Martijn D de Ruiter, Nadine J Meijboom, Jacobus P D van Veldhoven, Rongfang Liu, Willem Jespers, Gerard J P van Westen, Laura H Heitman, Adriaan P IJzerman, Daan van der Es","doi":"10.1007/s11302-024-10026-x","DOIUrl":"10.1007/s11302-024-10026-x","url":null,"abstract":"<p><p>The human equilibrative nucleoside transporter 1 (SLC29A1, hENT1) is a solute carrier that modulates the passive transport of nucleosides and nucleobases, such as adenosine. This nucleoside regulates various physiological processes, such as vasodilation and -constriction, neurotransmission and immune defense. Marketed drugs such as dilazep and dipyridamole have proven useful in cardiovascular afflictions, but the application of hENT1 inhibitors can be beneficial in a number of other diseases. In this study, 39 derivatives of dilazep's close analogue ST7092 were designed, synthesized and subsequently assessed using [³H]NBTI displacement assays and molecular docking. Different substitution patterns of the trimethoxy benzoates of ST7092 reduced interactions within the binding pocket, resulting in diminished hENT1 affinity. Conversely, [³H]NBTI displacement by potentially covalent compounds 14b, 14c, and 14d resulted in high affinities (K_i values between 1.1 and 17.5 nM) for the transporter, primarily by the ability of accommodating the inhibitors in various ways in the binding pocket. However, any indication of covalent binding with amino acid residue C439 remained absent, conceivably as a result of decreased nucleophilic residue reactivity. In conclusion, this research introduces novel dilazep derivatives that are active as hENT1 inhibitors, along with the first high affinity dilazep derivatives equipped with an electrophilic warhead. These findings will aid the rational and structure-based development of novel hENT1 inhibitors and pharmacological tools to study hENT1's function, binding mechanisms, and its relevance in (patho)physiological conditions.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"289-316"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ENTPD1 (CD39) and NT5E (CD73) expression in human medulloblastoma: an in silico analysis.","authors":"Marco Antônio Stefani, Elizandra Braganhol, Guilherme Tomasi Santos, Samuel Masao Suwa, Daiane Dias Cabeleira, Guilherme Pamplona Bueno de Andrade","doi":"10.1007/s11302-024-10035-w","DOIUrl":"10.1007/s11302-024-10035-w","url":null,"abstract":"<p><p>Medulloblastoma is the most common malignant tumor in the pediatric population. Its classification has incorporated key molecular variations alongside histological characterization. CD39 (also known as ENTPD1) and CD73 (also known as NT5E), enzymes of the purinergic signaling pathway, act in synergy to generate extracellular adenosine, creating an immunosuppressive tumor microenvironment. Our study examined the expression of mRNA of these genes in previously described transcriptome data sets of medulloblastoma patient samples from the Cavalli Cohort (n = 763). Survival distribution was estimated according to the Kaplan-Meier method using a median cut-off and log-rank statistics (p ≤ 0.05). In non-WNT and non-SHH medulloblastoma Group 4 (n = 264), the high expression of ENTPD1 and NT5E was significantly related to a lower overall survival (p = 2.7e-04; p = 2.6e-03). In the SHH-activated group (n = 172), the high expression of ENTPD1 was significantly related to lower overall survival (p = 7.8e-03), while the high expression of NT5E was significantly related to greater overall survival (p = 0.017). In the WNT group (n = 63), the expressions of ENTPD1 and NT5E were not significantly correlated with overall survival (p = 0.212; p = 0.101). In non-WNT and non-SHH medulloblastoma Group 3 (n = 113), the high expression of ENTPD1 was significantly related to greater survival (p = 0.034), while expression of NT5E was not significantly related to survival of patients (p = 0.124). This in silico analysis indicates that ENTPD1 (CD39) and NT5E (CD73) can be seen as potential prognostic markers and therapeutic targets for primary medulloblastomas in non-WNT and non-SHH Group 4.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"331-337"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Honouring Geoff Burnstock.","authors":"Yong Tang, Peter Illes, Charles Kennedy","doi":"10.1007/s11302-024-10061-8","DOIUrl":"10.1007/s11302-024-10061-8","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"195"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of purinergic system components in the venom of Bothrops mattogrossensis and the inhibitory effect of specioside extracted from Tabebuia aurea.","authors":"Dhébora Albuquerque Dias, Kamylla Fernanda Souza de Souza, Iluska Senna Bonfá Moslaves, Marcus Vinicius Buri, Denise Caroline Luiz Soares Basilio, Isabelly Teixeira Espinoça, Eduardo Benedetti Parisotto, Saulo Euclides Silva-Filho, Ludovico Migliolo, Jeandre Augusto Otsubo Jaques, Daniel Guerra Franco, Ana Marisa Chudzinski-Tavassi, Paula Helena Santa Rita, Denise Brentan da Silva, Carlos Alexandre Carollo, Mônica Cristina Toffoli-Kadri, Edgar Julian Paredes-Gamero","doi":"10.1007/s11302-024-10032-z","DOIUrl":"10.1007/s11302-024-10032-z","url":null,"abstract":"<p><p>Snake bites are a severe problem in the countryside of Brazil and are usually attributed to snakes of the genera Bothrops, Crotalus, and Lachesis. Snake venom can release ectoenzymes and nucleotidases that modulate the purinergic system. In addition to serum therapy against snake poisoning, medicinal plants with anti-inflammatory activities, such as Tabebuia aurea, is empirically applied in accidents that occur in difficult-to-access areas. This study aimed was to verify the presence and activity of nucleotidases in the crude venom of Bothrops mattogrossensis (BmtV) in vitro and characterize the modulation of purinergic components, myeloid differentiation, and inflammatory/oxidative stress markers by BmtV in vivo and in vitro. Moreover, our study assessed the inhibitory activities of specioside, an iridoid isolated from Tabebuia aurea, against the effects of BmtV. Proteomic analysis of venom content and nucleotidase activity confirm the presence of ectonucleotidase-like enzymes in BmtV. In in vivo experiments, BmtV altered purinergic component expression (P2X7 receptor, CD39 and CD73), increased neutrophil numbers in peripheral blood, and elevated oxidative stress/inflammatory parameters such as lipid peroxidation and myeloperoxidase activity. BmtV also decreased viability and increased spreading index and phagocytic activity on macrophages. Specioside inhibited nucleotidase activity, restored neutrophil numbers, and mediate the oxidative/inflammatory effects produced by BmtV. We highlight the effects produced by BmtV in purinergic system components, myeloid differentiation, and inflammatory/oxidative stress parameters, while specioside reduced the main BmtV-dependent effects.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"317-329"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2Y₁₁ receptor is a critical regulator of extracellular ATP-mediated premature senescence in lung fibroblasts: Implications of ER-Ca⁺² release/mitochondrial ROS production signaling pathway.","authors":"Abdel-Aziz S Shatat","doi":"10.1007/s11302-024-10036-9","DOIUrl":"10.1007/s11302-024-10036-9","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"271-273"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Adventures in translation.","authors":"Bruce Cronstein, Siddhesh R Angle","doi":"10.1007/s11302-025-10085-8","DOIUrl":"10.1007/s11302-025-10085-8","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"199"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A_2B adenosine receptor signaling and regulation.","authors":"Zhan-Guo Gao, Mansour Haddad, Kenneth A Jacobson","doi":"10.1007/s11302-024-10025-y","DOIUrl":"10.1007/s11302-024-10025-y","url":null,"abstract":"<p><p>The A_2B adenosine receptor (A_2BR) is one of the four adenosine-activated G protein-coupled receptors. In addition to adenosine, protein kinase C (PKC) was recently found to activate the A_2BR. The A_2BR is coupled to both G_s and G_i, as well as G_q proteins in some cell types. Many primary cells and cell lines, such as bladder and breast cancer, bronchial smooth muscle, skeletal muscle, and fat cells, express the A_2BR endogenously at high levels, suggesting its potentially important role in asthma, cancer, diabetes, and other conditions. The A_2BR has been characterized as both pro- and anti-inflammatory, inducing cell type-dependent secretion of IL-6, IL-8, and IL-10. Theophylline and enprofylline have long been used for asthma treatment, although it is still not entirely clear if their A_2BR antagonism contributes to their therapeutic effects or side effects. The A_2BR is required in ischemic cardiac preconditioning by adenosine. Both A_2BR and protein kinase C (PKC) contribute to cardioprotection, and both modes of A_2BR signaling can be blocked by A_2BR antagonists. Inhibitors of PKC and A_2BR are in clinical cancer trials. Sulforaphane and other isothiocyanates from cruciferous vegetables such as broccoli and cauliflower have been reported to inhibit A_2BR signaling via reaction with an intracellular A_2BR cysteine residue (C210). A full, A_2BR-selective agonist, critical to elucidate many controversial roles of the A_2BR, is still not available, although agonist-bound A_2BR structures have recently been reported.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"201-220"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATP release mediated by pannexin-3 is required for plasma cell survival via P2X4 receptors in bone marrow.","authors":"Sonia Paz-López","doi":"10.1007/s11302-024-10024-z","DOIUrl":"10.1007/s11302-024-10024-z","url":null,"abstract":"","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":"267-269"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}