IUBMB Life最新文献

{"title":"Thiouracil and triazole conjugate induces autophagy through the downregulation of Wnt/β-catenin signaling pathway in human breast cancer cells","authors":"Bada Yoon,&nbsp;Basappa Basappa,&nbsp;Shreeja Basappa,&nbsp;Omantheswara Nagaraju,&nbsp;Mahendra Madegowda,&nbsp;K. S. Rangappa,&nbsp;Gautam Sethi,&nbsp;Kwang Seok Ahn","doi":"10.1002/iub.2917","DOIUrl":"10.1002/iub.2917","url":null,"abstract":"<p>Autophagy is vital for maintaining cellular homeostasis by breaking down unnecessary organelles and proteins within cells. Its activity varies abnormally in several diseases, including cancer, making it a potential target for therapeutic strategies. The Wnt/β-catenin signaling pathway significantly impacts cancer by stabilizing β-catenin protein and promoting the transcription of its target genes. Therefore, we aimed to identify candidate substances targeting this signaling pathway. We designed and tested a thiouracil conjugate, discovering that TTP-8 had anti-tumor effects on human breast cancer cell lines MCF-7 and MDA-MB231. Our findings showed that TTP-8 upregulated the expression of LC3 protein, a marker of autophagy in breast cancer cells, suggesting that TTP-8 might induce autophagy. Further analysis confirmed an increase in autophagy-related proteins, with consistent results obtained from flow cytometry and confocal microscopy. Interestingly, the induction of LC3 expression by TTP-8 was even more pronounced in MCF-7 and MDA-MB231 cells transfected with β-catenin siRNA. Thus, our research supports the idea that the Wnt/β-catenin signaling pathway influences the regulation of autophagy-related proteins, thereby inducing autophagy. This suggests that TTP-8 could serve as a novel agent for treating breast cancer.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1377-1391"},"PeriodicalIF":3.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.2917","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AARS Online: A collaborative database on the structure, function, and evolution of the aminoacyl-tRNA synthetases","authors":"Jordan Douglas,&nbsp;Haissi Cui,&nbsp;John J. Perona,&nbsp;Oscar Vargas-Rodriguez,&nbsp;Henna Tyynismaa,&nbsp;Claudia Alvarez Carreño,&nbsp;Jiqiang Ling,&nbsp;Lluís Ribas de Pouplana,&nbsp;Xiang-Lei Yang,&nbsp;Michael Ibba,&nbsp;Hubert Becker,&nbsp;Frédéric Fischer,&nbsp;Marie Sissler,&nbsp;Charles W. Carter Jr,&nbsp;Peter R. Wills","doi":"10.1002/iub.2911","DOIUrl":"10.1002/iub.2911","url":null,"abstract":"<p>The aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various translational and non-translational activities beyond aminoacylation, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the 22 coded amino acids are handled by 16 evolutionary families of Class I aaRS and 21 families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia-like tool curated by an international consortium of field experts. This platform systematizes existing knowledge about the aaRS by showcasing a taxonomically diverse selection of aaRS sequences and structures. Through its graphical user interface, AARS Online facilitates a seamless exploration between protein sequence and structure, providing a friendly introduction to the material for non-experts and a useful resource for experts. Curated multiple sequence alignments can be extracted for downstream analyses. Accessible at www.aars.online, AARS Online is a free resource to delve into the world of the aaRS.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1091-1105"},"PeriodicalIF":3.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia synchronizes with the circadian rhythm of the glymphatic system and modulates glymphatic system function","authors":"Ting Yang,&nbsp;Yan Tang,&nbsp;Xinghua Liu,&nbsp;Song Gong,&nbsp;Ensheng Yao","doi":"10.1002/iub.2903","DOIUrl":"10.1002/iub.2903","url":null,"abstract":"<p>Microglia, as immune cells in the central nervous system, possess the ability to adapt morphologically and functionally to their environment. Glymphatic system, the principal waste clearance system in the brain, exhibits circadian rhythms. However, the impact of microglia on the glymphatic system function remains unknown. In this study, we explored the intricate relationship between microglia and the glymphatic system. Examining diurnal patterns, we identified synchronized behaviors in glymphatic activity and microglial morphology, peaking during sleep and exhibiting distinct changes in branching complexity. Depleting microglia using PLX5622 or in P2Y12 knockout mice enhanced glymphatic function. Chemogenetic manipulation of microglia demonstrated that activating HM3D improved glymphatic function, while inhibiting HM4D unexpectedly increased microglial complexity. These findings highlight the dynamic influence of microglia on the glymphatic system.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1209-1222"},"PeriodicalIF":3.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin effect on breast and ovarian cancers by targeting the PI3K/Akt/mTOR pathway","authors":"Vahid Pourbarkhordar,&nbsp;Sohrab Rahmani,&nbsp;Ali Roohbakhsh,&nbsp;A. Wallace Hayes,&nbsp;Gholamreza Karimi","doi":"10.1002/iub.2900","DOIUrl":"10.1002/iub.2900","url":null,"abstract":"<p>Melatonin, the hormone of the pineal gland, possesses a range of physiological functions, and recently, its anticancer effect has become more apparent. A more thorough understanding of molecular alterations in the components of several signaling pathways as new targets for cancer therapy is needed because of current innate restrictions such as drug toxicity, side effects, and acquired or de novo resistance. The PI3K/Akt/mTOR pathway is overactivated in many solid tumors, such as breast and ovarian cancers. This pathway in normal cells is essential for growth, proliferation, and survival. However, it is an undesirable characteristic in malignant cells. We have reviewed multiple studies about the effect of melatonin on breast and ovarian cancer, focusing on the PI3K/Akt/mTOR pathway. Melatonin exerts its inhibitory effects via several mechanisms. A: Downregulation of downstream or upstream components of the signaling pathway such as phosphatase and tensin homolog (PTEN), phosphatidylinositol (3,4,5)-trisphosphate kinase (PI3K), p-PI3K, Akt, p-Akt, mammalian target of rapamycin (mTOR), and mTOR complex1 (mTORC1). B: Apoptosis induction by decreasing MDM2 expression, a downstream target of Akt, and mTOR, which leads to Bad activation in addition to Bcl-XL and p53 inhibition. C: Induction of autophagy in cancer cells via activating ULK1 after mTOR inhibition, resulting in Beclin-1 phosphorylation. Beclin-1 with AMBRA1 and VPS34 promotes PI3K complex I activity and autophagy in cancer cells. The PI3K/Akt/mTOR pathway overlaps with other intracellular signaling pathways and components such as AMP-activated protein kinase (AMPK), Wnt/β-catenin, mitogen-activated protein kinase (MAPK), and other similar pathways. Cancer therapy can benefit from understanding how these pathways interact and how melatonin affects these pathways.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1035-1049"},"PeriodicalIF":3.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lectins CGL and MTL, representatives of mytilectin family, exhibit different antiproliferative activity in Burkitt's lymphoma cells","authors":"Alexandra S. Kuzmich,&nbsp;Alina P. Filshtein,&nbsp;Galina N. Likhatskaya,&nbsp;Tatiana Y. Gorpenchenko,&nbsp;Irina V. Chikalovets,&nbsp;Tatyana O. Mizgina,&nbsp;Kuo-Feng Hua,&nbsp;Gunhild von Amsberg,&nbsp;Sergey A. Dyshlovoy,&nbsp;Oleg V. Chernikov","doi":"10.1002/iub.2909","DOIUrl":"10.1002/iub.2909","url":null,"abstract":"<p>Lectins are carbohydrate-binding proteins, whose biological effects are exerted via binding to glycoconjugates expressed on the surface of cells. Exposure to lectins can lead not only to a change in the structure and properties of cells but also to their death. Here, we studied the biological activity of lectins from the mussels <i>Crenomytilus graynus</i> (CGL) and <i>Mytilus trossulus</i> (MTL) and showed that these proteins can affect the proliferation of human lymphoma cells. Both lectins suppressed the formation of colonies as well as cell cycle progression. The mechanism of action of these lectins was not mediated by reactive oxygen species but included damaging of mitochondria, inhibition of key cell cycle points, and activation of MAPK signaling pathway in tumor cells. Computer modeling suggested that various effects of CGL and MTL on lymphoma cells may be due to the difference in the energy of binding of these lectins to carbohydrate ligands on the cell surface. Thus, molecular recognition of residues of terminal carbohydrates on the surface of tumor cells is a key factor in the manifestation of the biological action of lectins.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1279-1294"},"PeriodicalIF":3.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of resveratrol through modulation of PI3K/Akt/GSK-3β pathway and metalloproteases","authors":"Lütfiye Ozpak,&nbsp;Bakiye Göker Bağca","doi":"10.1002/iub.2902","DOIUrl":"10.1002/iub.2902","url":null,"abstract":"<p>To analyze the expressional changes in the PI3K/Akt/GSK-3β pathway and metalloprotease in the cellular Alzheimer's Disease (AD) model with the effect of antioxidant resveratrol. Neuron-like cells were obtained by a two-step method of neuronal differentiation by using a combination of retinoic acid (RA) and brain-derived factor (BDNF) exposure. Then, the application of the amyloid beta peptide 25–35 (Aβ25-35) to the cell culture mimicked the environmental toxicity observed in AD. Afterward, cell viability and apoptosis assays were performed to determine whether the resveratrol exerts a cytotoxic and apoptotic effect. Finally, the expressional changes in genes in the cellular AD model with the effect of resveratrol were analyzed by Real-Time PCR. The analysis in silico was assessed using the STRING V12.0 database in each group. Apoptosis data findings were decreased by 1.5-fold and 2.5-fold respectively by Differentiated+Resveratrol (RES) and RES when compared to control but no significant difference was observed between RES and AD model groups. Real-time PCR analysis results revealed PI3K (3.38-fold), AKT (3.95-fold), and RELN (1.99-fold) expressions were significantly higher (<i>p</i> &lt; .001), and also GSK-3β, TAU, ADAMTS-4, ADAMTS-5, and TIMP-3 gene expression levels were significantly downregulated (2.53-, 1.79-, 2.85-, 4.09-, and 6.62-fold, respectively) in the Differentiated+Aβ + RES groups compared to the Differentiated+Aβ group (<i>p</i> &lt; .001). Network analysis shows the functional enrichment of 23 Alzheimer-related GO terms in the Wnt signaling, proteolysis, and extracellular matrix organization pathways. Resveratrol has inhibited GSK-3β by activating the PI3K/Akt insulin pathway in a neurotoxic environment. In addition, TAU, RELN, metalloproteases, and their inhibitors associated with Alzheimer's pathology have been regulated supporting the neuroprotective effect of resveratrol.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1199-1208"},"PeriodicalIF":3.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin alleviates the pyroptosis of β cells in T2DM by inhibiting NLRP3 inflammasome through regulating miR-19b-3p/SOCS3/STAT3 axis mediated autophagy","authors":"Jingjing Yang,&nbsp;Anjun Tan,&nbsp;Tianrong Li,&nbsp;Hewen Chen","doi":"10.1002/iub.2907","DOIUrl":"10.1002/iub.2907","url":null,"abstract":"<p>The purpose of this study was to analyze the mechanism by which irisin affects β-cell pyroptosis in type 2 diabetes mellitus (T2DM). The in vivo T2DM model was established by raised with high-fat diet and intraperitoneally injection of streptozocin. Min6 cells were divided into four groups: negative control (NC), high glucose (HG), HG + irisin, and HG + irisin+3-MA. The cell viability was determined by CCK-8 assay. Dual-luciferase gene reporter assay was conducted to confirm the binding between miR-19b-3p and SOCS3. The expression level of FNDC5 and GSDMD was visualized using the immunofluorescence assay. The protein level of FNDC5, Beclin1, LC3II/I, NLRP3, cleaved-caspase-1, GSDMD-N, STAT3, p-STAT3, and SOCS3 was determined by Western blotting. The secretion of irisin, lactate dehydrogenase (LDH), and insulin was checked by ELISA. In vivo results showed that pathological changes in islet tissues with declined number of β cells, elevated FBG value, decreased FIN and HOMA-β value, elevated autophagy-associated proteins expressions, and activated NLRP3 signaling in T2DM mice, which were dramatically reversed by FNDC5 overexpression. Furthermore, the declined level of miR-19b-3p and p-STAT3, as well as the upregulation of SOCS3, was greatly rescued by FNDC5 overexpression. The in vitro data confirmed the binding site between SOCS3 and miR-19b-3p. SOCS3 was downregulated and p-STAT3 was upregulated in miR-19b-3p mimic-treated Min6 cells. In HG-stimulated Min6 cells, the elevated cell viability, increased production of insulin, decreased release of LDH, and inactivated NLRP3 signaling induced by irisin were abolished by miR-19b-3p inhibitor and STAT3 inhibitor. The increased level of autophagy-related proteins and activated SOCS3/STAT3 axis induced by irisin in HG-stimulated Min6 cells were abolished by miR-19b-3p inhibitor. The inhibitory effect of irisin against NLRP3 signaling in HG-stimulated Min6 cells was abrogated by 3-MA. In conclusion, irisin alleviated the pyroptosis of β cells in T2DM by inhibiting NLRP3 signaling through miR-19b-3p/SOCS3/STAT3 axis mediated autophagy.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1264-1278"},"PeriodicalIF":3.7,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of transglutaminase 2 inhibits ionizing radiation-induced cellular senescence in skin keratinocytes in vitro","authors":"Juping Chen,&nbsp;Jiang Ma,&nbsp;Dandan Qi,&nbsp;Yuxuan Wang,&nbsp;Xiaoming Sun,&nbsp;Jinghui Yang,&nbsp;Wentao Sun,&nbsp;Changjiao Luan,&nbsp;Qing Shan,&nbsp;Weili Liu,&nbsp;Xingjie Ma","doi":"10.1002/iub.2906","DOIUrl":"10.1002/iub.2906","url":null,"abstract":"<p>Senescent cells are typically characterized by a stable proliferation arrested in dividing cells accompanied with a senescence-associated secretory phenotype (SASP). Skin cellular senescence is the primary cause of skin aging, whereas the lack of identified skin senescence markers limits our understanding of the mechanisms involved in skin aging. Recent studies have revealed that intracellular calcium signaling has emerged as a key player in regulating cellular senescence and aging. However, the implication and roles of calcium signaling in skin keratinocyte senescence remain only partially understood. In this study, we developed a model for skin keratinocyte senescence using ionizing radiation (I/R) stimulation and found that the calcium-associated gene transglutaminase 2 (<i>TGM2</i>) was significantly induced compared with normal control. Interestingly, inhibition of TGM2 was found to delay skin keratinocyte senescence by suppressing I/R-promoted intracellular calcium signaling, accumulation of reactive oxygen species (ROS), DNA damage, as well as NF-κB-mediated SASP secretion. Taken together, our findings demonstrate that inhibition of TGM2 contributes to bypassing I/R-induced skin keratinocyte senescence and sheds light on novel strategies against skin stresses caused by I/R.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1252-1263"},"PeriodicalIF":3.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD38/cADPR-mediated calcium signaling in a human myometrial smooth muscle cell line, PHM1","authors":"Soner Dogan,&nbsp;Timothy F. Walseth,&nbsp;Bilge Guvenc Tuna,&nbsp;Eda Uçar,&nbsp;Mathur S. Kannan,&nbsp;Deepak A. Deshpande","doi":"10.1002/iub.2904","DOIUrl":"10.1002/iub.2904","url":null,"abstract":"<p>Cyclic ADP-ribose (cADPR) has emerged as a calcium-regulating second messenger in smooth muscle cells. CD38 protein possesses ADP-ribosyl cyclase and cADPR hydrolase activities and mediates cADPR synthesis and degradation. We have previously shown that CD38 expression is regulated by estrogen and progesterone in the myometrium. Considering hormonal regulation in gestation, the objective of the present study was to determine the role of CD38/cADPR signaling in the regulation of intracellular calcium upon contractile agonist stimulation using immortalized pregnant human myometrial (PHM1) cells. Western blot, immunofluorescence, and biochemical studies confirmed CD38 expression and the presence of ADP-ribosyl cyclase (2.6 ± 0.1 pmol/mg) and cADPR hydrolase (26.8 ± 6.8 nmoles/mg/h) activities on the PHM1 cell membrane. Oxytocin, PGF_2α, and ET-1 elicited [Ca²⁺]_i responses, and 8-Br-cADPR, a cADPR antagonist significantly attenuated agonist-induced [Ca²⁺]_i responses between 20% and 46% in average. The findings suggest that uterine contractile agonists mediate their effects in part through CD38/cADPR signaling to increase [Ca²⁺]_i and presumably uterine contraction. As studies in humans are limited by the availability of myometrium from healthy donors, PHM1 cells form an in vitro model to study human myometrium.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1223-1233"},"PeriodicalIF":3.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular adenosine oppositely regulates the purinome machinery in glioblastoma and mesenchymal stem cells","authors":"Deborah Pietrobono,&nbsp;Lara Russo,&nbsp;Maria Sofia Bertilacchi,&nbsp;Laura Marchetti,&nbsp;Claudia Martini,&nbsp;Chiara Giacomelli,&nbsp;Maria Letizia Trincavelli","doi":"10.1002/iub.2905","DOIUrl":"10.1002/iub.2905","url":null,"abstract":"<p>Glioblastoma (GB) is a lethal brain tumor that rapidly adapts to the dynamic changes of the tumor microenvironment (TME). Mesenchymal stem/stromal cells (MSCs) are one of the stromal components of the TME playing multiple roles in tumor progression. GB progression is prompted by the immunosuppressive microenvironment characterized by high concentrations of the nucleoside adenosine (ADO). ADO acts as a signaling molecule through adenosine receptors (ARs) but also as a genetic and metabolic regulator. Herein, the effects of high extracellular ADO concentrations were investigated in a human glioblastoma cellular model (U343MG) and MSCs. The modulation of the purinome machinery, i.e., the ADO production (CD39, CD73, and adenosine kinase [ADK]), transport (equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2)), and degradation (adenosine deaminase [ADA]) were investigated in both cell lines to evaluate if ADO could affect its cell management in a positive or negative feed-back loop. Results evidenced a different behavior of GB and MSC cells upon exposure to high extracellular ADO levels: U343MG were less sensitive to the ADO concentration and only a slight increase in ADK and ENT1 was evidenced. Conversely, in MSCs, the high extracellular ADO levels reduced the ADK, ENT1, and ENT2 expression, which further sustained the increase of extracellular ADO. Of note, MSCs primed with the GB-conditioned medium or co-cultured with U343MG cells were not affected by the increase of extracellular ADO. These results evidenced how long exposure to ADO could produce different effects on cancer cells with respect to MSCs, revealing a negative feedback loop that can support the GB immunosuppressive microenvironment. These results improve the knowledge of the ADO role in the maintenance of TME, which should be considered in the development of therapeutic strategies targeting adenosine pathways as well as cell-based strategies using MSCs.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1234-1251"},"PeriodicalIF":3.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}