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Recombinant ADAMTS1 promotes muscle cell differentiation and alleviates muscle atrophy by repressing NOTCH1. 重组 ADAMTS1 通过抑制 NOTCH1 促进肌肉细胞分化并缓解肌肉萎缩。
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-12-01
Sang Hyup Lee, Sang Yoon Kim, Yun Gu Gwon, Chanwoo Lee, Changhwan Kim, Ick Hyun Cho, Tae-Won Kim, Bong-Keun Choi
{"title":"Recombinant ADAMTS1 promotes muscle cell differentiation and alleviates muscle atrophy by repressing NOTCH1.","authors":"Sang Hyup Lee, Sang Yoon Kim, Yun Gu Gwon, Chanwoo Lee, Changhwan Kim, Ick Hyun Cho, Tae-Won Kim, Bong-Keun Choi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) plays crucial roles in various biological processes, including myogenesis, by modulating the neurogenic locus notch homolog protein 1 (NOTCH1) signaling pathway. However, the mechanisms through which ADAMTS1 regulates myogenesis remain unclear. In this study, we generated recombinant ADAMTS1 mutants and determined their effects on muscle cell differentiation, focusing on the regulation of NOTCH1 signaling. Treatment of C2C12 cells with recombinant ADAMTS1 protein enhanced muscle cell differentiation. Meanwhile, ADAM10 treatment inhibited muscle differentiation through the activation of NOTCH1 cleavage. Recombinant ADAMTS1 reversed ADAM10-induced muscle cell atrophy by suppressing NOTCH1 activation and downregulating its target gene. Recombinant ADAMTS1 also alleviated dexamethasoneinduced muscle atrophy in a mouse model. In summary, our findings suggest that recombinant ADAMTS1 promotes muscle regeneration by suppressing NOTCH1 and highlight the potential of recombinant ADAMTS1 proteins in the treatment of muscle wasting disease. [BMB Reports 2024; 57(12): 539-545].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"539-545"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680671","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}
引用次数: 0
Targeting proprotein convertase subtilisin/kexin type 7 in macrophages as a therapeutic strategy to mitigate myocardial infarction-induced inflammation. 巨噬细胞中靶向蛋白转化酶枯草素/kexin 7作为缓解心肌梗死诱导炎症的治疗策略
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-12-01
Shin Hye Moon, Inyoung Chung, Na Hyeon Yoon, Jing Jin, Hyae Yon Kweon, Won Kee Yoon, Nabil G Seidah, Goo Taeg Oh
{"title":"Targeting proprotein convertase subtilisin/kexin type 7 in macrophages as a therapeutic strategy to mitigate myocardial infarction-induced inflammation.","authors":"Shin Hye Moon, Inyoung Chung, Na Hyeon Yoon, Jing Jin, Hyae Yon Kweon, Won Kee Yoon, Nabil G Seidah, Goo Taeg Oh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Myocardial infarction (MI), a major form of coronary artery disease (CAD), triggers a severe inflammatory response in the heart, resulting in increased cell death and adverse ventricular remodeling. Despite treatment advancements, MI remains a significant risk factor for heart failure, underscoring the necessity for a more in-depth exploration of immune cell mechanisms. Proprotein convertase subtilisin/kexin type 7 (PCSK7), expressed in various tissues and immune cells, has been implicated in cardiovascular disease, yet its specific role in cardiac immune cells remains poorly understood. This study aimed to elucidate the role of PCSK7 in MI-related inflammation. Our findings indicate that PCSK7 deficiency reduces circulating cholesterol levels, potentially mitigating infarct injury and improving cardiac function by modulating immune cells. Additionally, PCSK7 promotes macrophage activation and lipid uptake at the ischemic site, intensifying the pathology. We also observed that PCSK7 activates the TNF-α/JNK signaling pathway in macrophages intracellularly, amplifying the inflammatory response. Therefore, targeting PCSK7 in macrophages could help mitigate post-MI inflammation, alleviate disease severity, and offer novel therapeutic strategies for patients with CAD. [BMB Reports 2024; 57(12): 553-558].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"553-558"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765884","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}
引用次数: 0
Specialized pro-resolving mediator 7S MaR1 inhibits IL-6 expression via modulating ROS/p38/ERK/NF-κB pathways in PM10-exposed keratinocytes. 通过调节 PM10 暴露角质细胞中的 ROS/p38/ERK/NF-κB 通路,特化的促溶解介质 7S MaR1 可抑制 IL-6 的表达。
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-11-01
Jinju Kim, Hyo-Min Park, Chae-Min Lim, Kyeong-Bae Jeon, Seonhwa Kim, Jin Lee, Jin Lee, Jin-Tae Hong, Deok-Kun Oh, Young Yang, Do-Young Yoon
{"title":"Specialized pro-resolving mediator 7S MaR1 inhibits IL-6 expression via modulating ROS/p38/ERK/NF-κB pathways in PM<sub>10</sub>-exposed keratinocytes.","authors":"Jinju Kim, Hyo-Min Park, Chae-Min Lim, Kyeong-Bae Jeon, Seonhwa Kim, Jin Lee, Jin Lee, Jin-Tae Hong, Deok-Kun Oh, Young Yang, Do-Young Yoon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Keratinocytes are susceptible to airborne particulate matter (PM) exposure, resulting in human skin barrier dysfunction. Therefore, it is important to find useful reagents to resolve skin damages caused by PM. Here, we explored the protective effect of 7S MaR1, a specialized pro-resolving mediator derived from docosahexaenoic acid, on skin inflammation and the oxidative stress induced by PM with a diameter 10 μm or less (PM10) in human keratinocyte HaCaT cells. Interestingly, PM10-induced ROS generation was modulated by 7S MaR1 via the recovery of ROS scavenger genes. 7S MaR1 reduced PM10-induced IL-6 expression via modulating the p38/ERK/NF-κB signaling pathways. These results demonstrate that PM<sub>10</sub> induces inflammatory cytokines, which can lead to skin diseases. In addition, 7S MaR1 can resolve inflammation caused by PM<sub>10</sub>-induced oxidative stress and inflammatory cytokines. [BMB Reports 2024; 57(11): 490-496].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"490-496"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387641","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}
引用次数: 0
Differential roles of N- and C-terminal LIR motifs in the catalytic activity and membrane targeting of RavZ and ATG4B proteins. N 端和 C 端 LIR 基团在 RavZ 和 ATG4B 蛋白的催化活性和膜靶向性中的不同作用。
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-11-01
Sang-Won Park, Ju-Hui Park, Haneul Choi, Pureum Jeon, Seung-Hwan Lee, Won-Dong Shin, Hun-Joo Kim, Jin-A Lee, Deok-Jin Jang
{"title":"Differential roles of N- and C-terminal LIR motifs in the catalytic activity and membrane targeting of RavZ and ATG4B proteins.","authors":"Sang-Won Park, Ju-Hui Park, Haneul Choi, Pureum Jeon, Seung-Hwan Lee, Won-Dong Shin, Hun-Joo Kim, Jin-A Lee, Deok-Jin Jang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mammalian ATG8 proteins (mATG8s) are essential for selective autophagy because they recruit various proteins with LC3- interacting region (LIR) motifs to autophagic membranes. The RavZ protein, secreted by Legionella pneumophila, and mammalian ATG4B possess functional LIR motifs that participate in lipidated mATG8 deconjugation on autophagic membranes. RavZ comprises three functional LIR motifs at the N- and Cterminal sides of its catalytic domain (CAD). This study demonstrated that LIR motifs at the N-terminal side of the CAD of RavZ are involved in autophagic membrane targeting and substrate recognition, while LIR motif at the C-terminal side facilitate autophagic membrane targeting. Our results also revealed that the C-terminal LIR motif in human ATG4B is pivotal in delipidating LC3B-phosphatidylethanolamine (PE), but it plays a minor role in pro-LC3B priming in the cytosol. Therefore, introducing a functional LIR motif to the N-terminal of ATG4B does not affect LC3B-PE delipidation. This study clearly described the position-dependent roles of LIR motifs in RavZ and ATG4B in cellular contexts. [BMB Reports 2024; 57(11): 497-502].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"497-502"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387640","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}
引用次数: 0
Fluorescence-based techniques for investigating estrogen receptor dynamics. 基于荧光的雌激素受体动态研究技术。
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-11-01
Kiseok Han, Gyuho Choi, Tae-Jin Kim
{"title":"Fluorescence-based techniques for investigating estrogen receptor dynamics.","authors":"Kiseok Han, Gyuho Choi, Tae-Jin Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Understanding estrogen receptor (ER) signaling pathways is crucial for uncovering the mechanisms behind estrogen-related diseases, such as breast cancer, and addressing the effects of environmental estrogenic disruptors. Traditionally, ER signaling involves genomic events, including ligand binding, receptor dimerization, and transcriptional modulation within cellular nuclei. However, recent research have revealed ERs also participate in non-genomic signaling pathways, adding complexity to their functions. Researchers use advanced fluorescence-based techniques, leveraging fluorescent probes (FPb) to study ER dynamics in living cells, such as spatial distribution, expression kinetics, and functional activities. This review systematically examines the application of fluorescent probes in ER signaling research, covering the visualization of ER, ligandreceptor interactions, receptor dimerization, estrogen response elements (EREs)-mediated transcriptional activation, and G-proteincoupled estrogen receptor (GPER) signaling. Our aim is to provide researchers with valuable insights for employing FPb in their explorations of ER signaling. [BMB Reports 2024; 57(11): 472-483].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"472-483"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104037","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}
引用次数: 0
Characterization of an orthotopic mouse transplant model reveals early changes in the tumor microenvironment of lung cancer. 正位小鼠移植模型的特征揭示了肺癌肿瘤微环境的早期变化。
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-11-01
Minsu Na, Huiram Kang, Nayoung Kim, Areum Jo, Hae-Ock Lee
{"title":"Characterization of an orthotopic mouse transplant model reveals early changes in the tumor microenvironment of lung cancer.","authors":"Minsu Na, Huiram Kang, Nayoung Kim, Areum Jo, Hae-Ock Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To understand the cellular and molecular dynamics in the early stages of lung cancer, we explored a mouse model of orthotopic tumor transplant created from the Lewis Lung Carcinoma (LLC) cell line. Employing single-cell RNA sequencing, we analyzed the cellular landscape during tumor engraftment, focusing particularly on LLC cells harboring the Kras G12C mutation. This allowed us to identify LLC tumor cells via the detection of mutant Kras transcripts and observe elevated levels of Myc and mesenchymal gene expression. Moreover, our study revealed significant alterations in the lung microenvironment, including the activation of tissue remodeling genes in fibroblasts and the downregulation of MHC class II genes in myeloid subsets. Additionally, T/NK cell subsets displayed more regulatory phenotypes, coupled with reduced proliferation in CD8+ T cells. Collectively, these findings enhance our understanding of lung cancer progression, particularly in a tumor microenvironment with low immunogenicity. [BMB Reports 2024; 57(11): 484-489].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"484-489"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750979","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}
引用次数: 0
Stromal cells and epigenetics: emerging key players of chronic inflammatory skin diseases. 基质细胞和表观遗传学:慢性炎症性皮肤病的新兴关键角色。
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-11-01
Jihye Kim, Michael Detmar
{"title":"Stromal cells and epigenetics: emerging key players of chronic inflammatory skin diseases.","authors":"Jihye Kim, Michael Detmar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epigenetic alterations play a crucial role in developmental processes, tissue regeneration, and cellular differentiation. Epigenetic changes are dynamically reversible. Various drugs that target DNA methyltransferases or histone deacetylases have demonstrated their ability to restore normal epigenetic patterns in a number of diseases. While the involvement of epigenetic modifications has been identified in chronic inflammatory diseases, their specific impact on skin inflammation in stromal cells remains unclear. This mini-review explores the role of stromal cells in chronic inflammatory skin diseases, focusing on epigenetic modifications of stromal cells such as fibroblasts, lymphatic, and blood vascular endothelial cells in both healthy and diseased skin. We also provide an overview of recent findings that highlight the contribution of stromal cells, including fibroblasts, to inflammatory and remodeling processes through epigenetic changes in the context of chronic inflammatory conditions. Investigating epigenetic reprogramming of stromal cells might lead to novel strategies for treating chronic inflammatory skin diseases. [BMB Reports 2024; 57(11): 465-471].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"465-471"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104041","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}
引用次数: 0
Multifaceted roles of trained immunity in diverse pathological contexts. 训练有素的免疫力在不同病理情况下发挥着多方面的作用。
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-10-01
Hyo Jin Park, Su Min Kim, Un Yung Choi, Lark Kyun Kim
{"title":"Multifaceted roles of trained immunity in diverse pathological contexts.","authors":"Hyo Jin Park, Su Min Kim, Un Yung Choi, Lark Kyun Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Trained immunity, an innate immune response characterized by enhanced cellular responsiveness, exhibits a profound memory akin to adaptive immunity. This phenomenon involves intricate metabolic and epigenetic reprogramming triggered by stimuli such as β-glucan and BCG, shaping innate immune memory. Following elucidation of the background on trained immunity, it is important to explore its multifaceted roles in various pathological contexts. In this review, we delve into the specific contributions of trained immunity in the intricate landscape of viral infections, tumorigenesis, and diverse inflammatory diseases, shedding light on its potential as a therapeutic target, and offering comprehensive understanding of its broader immunological implications. [BMB Reports 2024; 57(10): 431-440].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"431-440"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247417","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}
引用次数: 0
The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1). 异三聚驱动蛋白-2 家族成员 KIF3A 可直接与残疾-1(Dab1)结合。
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-10-01
Myoung Hun Kim, Young Joo Jeong, Sang-Hwa Urm, Dae-Hyun Seog
{"title":"The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1).","authors":"Myoung Hun Kim, Young Joo Jeong, Sang-Hwa Urm, Dae-Hyun Seog","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The heterotrimeric molecular motor kinesin-2 is involved in the microtubule-dependent transport of intracellular cargo. It consists of two distinct motor subunits (KIF3A, and KIF3B) and a non-motor subunit, kinesin-associated protein 3 (KAP3). The cargo-binding domain (CBD) at the carboxyl (C)-terminus of KIF3s plays an important role in the interaction with several different binding proteins. To identify the binding proteins for heterotrimeric kinesin-2, we performed a yeast two-hybrid screen and found a new interaction with Disables-1 (Dab1), the intracellular adaptor protein of reelin receptors. Dab1 bound to the CBD of KIF3A, but did not interact with the C-terminal domain of KIF3B, KIF5B, KIF17 or KAP3. The phosphotyrosine binding (PTB) domain-containing region of Dab1 is essential for the interaction with KIF3A. KIF3A interacted with GST-Dab1, and GST-CaMKIIα, but did not interact with GST-apolipoprotein E receptor 2 (ApoER2)-C or with GST alone. When co-expressed in HEK-293T cells, Dab1 co-precipitated with KIF3A, but not with KIF5B. Dab1 and KIF3A were co-localized in cultured cells. We also identified deduced cell surface expression of ApoER2 in KIF3A dominant-negative cells. These results suggest that the KIF3A plays a role in the intracellular trafficking of ApoER2 to the cell surface. [BMB Reports 2024; 57(10): 447-452].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"447-452"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449628","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}
引用次数: 0
Inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human hepatocellular carcinoma. 抑制 P2RX7 可抑制糖酵解和 AKT 在人肝细胞癌中的激活,从而增加细胞毒性。
IF 2.9 3区 生物学
BMB Reports Pub Date : 2024-10-01
Jae Kook Yang, Junhyung Kim, Young Hyeon Ahn, Sang Ho Bae, Moo-Jun Baek, Sae Hwan Lee, Jong-Seok Moon
{"title":"Inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human hepatocellular carcinoma.","authors":"Jae Kook Yang, Junhyung Kim, Young Hyeon Ahn, Sang Ho Bae, Moo-Jun Baek, Sae Hwan Lee, Jong-Seok Moon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. HCC occurs people with chronic liver diseases. The purinergic receptor P2X 7 (P2RX7) is involved in tumor proliferation and growth. Also, P2RX7 is associated with tumor invasion and metastatic dissemination. High glucose utilization is important for the survival of various types of tumors. However, the role of P2RX7 in glucose metabolism and cellular survival of HCC remains unclear. Here, our results show that the gene and protein levels of P2RX7 were elevated in tumor cells of patients with HCC. The pharmacological inhibition of P2RX7 by A-804598, a selective P2RX7 antagonist, and genetic inhibition by P2RX7 knockdown suppressed the glycolytic activity by reduction of hexokinase 2 (HK2), a key enzyme of the glycolysis pathway, in human HCC cells. Also, both A-804598 treatment and P2RX7 knockdown induced cytotoxicity via inhibition of AKT activation which is critical for tumor cell survival in human HCC cells. Moreover, A-804598 treatment and P2RX7 knockdown increased cytotoxicity and caspase-3 activation in human HCC cells. These results suggest that inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human HCC. [BMB Reports 2024; 57(10): 459-464].</p>","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":" ","pages":"459-464"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104039","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}
引用次数: 0
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