Biochimica et biophysica acta. General subjects最新文献

{"title":"Tetrahydroquinoline/4,5-dihydroisoxazoline derivatives counteract multidrug resistance in cancer cells by inhibiting P-glycoprotein (ABCB1)-mediated transport","authors":"Marina Hembecker ,&nbsp;Diogo Henrique Kita ,&nbsp;Azam Rashidian ,&nbsp;Luis C. Vesga ,&nbsp;Bruna Estelita Ruginsk ,&nbsp;Arnold R. Romero Bohórquez ,&nbsp;Stelia Carolina Mendez-Sanchez ,&nbsp;Vinicius Goncalves Maltarollo ,&nbsp;Fabiane Gomes de Moraes Rego ,&nbsp;Geraldo Picheth ,&nbsp;Antti Poso ,&nbsp;Katalin Goda ,&nbsp;Suresh V. Ambudkar ,&nbsp;Vivian Rotuno Moure ,&nbsp;Thales Kronenberger ,&nbsp;Glaucio Valdameri","doi":"10.1016/j.bbagen.2025.130894","DOIUrl":"10.1016/j.bbagen.2025.130894","url":null,"abstract":"<div><div>Cancer treatment is challenged by the emergence of multidrug resistance (MDR). MDR is often caused by the overexpression of certain ABC transporters, such as P-glycoprotein (P-gp, ABCB1) in the plasma membrane of tumor cells and tumor stem cells. Inhibition of ABC transporter-mediated efflux of anticancer drugs might be a plausible approach to overcome MDR. Here, we studied the interaction of 16 tetrahydroquinoline/4,5-dihydroisoxazole derivatives (<strong>A1</strong> - <strong>D4</strong>) with human P-gp to identify and characterize new P-gp inhibitors. We found that compounds <strong>C1</strong> and <strong>D1</strong> inhibited the P-gp-mediated efflux of rhodamine 123 (R123), with IC₅₀ values of 41.5 and 6.6 μM, respectively. Both compounds showed low cytotoxicity on NIH3T3 and NIH3T3-<em>ABCB1</em> cells over a broad concentration range. Interestingly, <strong>C1</strong> and <strong>D1</strong> increased the ATPase activity of P-gp at sub-micromolar concentrations, showing EC₅₀ values of 0.17 and 0.62 μM, respectively. However, thermal inactivation and UIC2 reactivity assays supported that, similar to potent P-gp inhibitors, <strong>C1</strong> and <strong>D1</strong> can hinder the dimerization of the nucleotide binding domains (NBDs), when applied at higher concentrations (≥10 μM). In addition, docking studies showed that <strong>D1</strong> preferentially interacts with the central substrate binding cavity of P-gp. Finally, <strong>D1</strong> chemosensitized drug-resistant KB-V1 cells overexpressing P-gp. In view of our previous findings that <strong>C1</strong> and <strong>D1</strong> also inhibit ABCG2 and MRP1, they can be considered as novel pan-ABC transporter inhibitors offering potential for treating chemotherapy-resistant tumors.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130894"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696023","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":"β-Sitosterol extends lifespan and healthspan in Caenorhabditis elegans via multi-omics analysis of longevity, neuronal, and immune pathways","authors":"Thirumugam Gowripriya ,&nbsp;Annadurai Hariharan ,&nbsp;Radhakrishnan Yashwanth ,&nbsp;Bhaskar James Prabhanand ,&nbsp;Ramamurthi Suresh ,&nbsp;Koilmani Emmanuvel Rajan ,&nbsp;Jain Ankit ,&nbsp;Krishnaswamy Balamurugan","doi":"10.1016/j.bbagen.2025.130899","DOIUrl":"10.1016/j.bbagen.2025.130899","url":null,"abstract":"<div><div>β-Sitosterol, a naturally occurring plant sterol, has attracted significant interest due to its potential health benefits. This study investigates the molecular mechanisms through which β-sitosterol influences lifespan and healthspan in <em>C. elegans</em>. LC-MS analysis revealed that wide range of protein targets associated with longevity, neuronal regulation, and innate immunity pathways. <em>In vivo</em> experimental validation demonstrated that β-sitosterol significantly extended the lifespan of <em>C. elegans</em> by downregulating critical aging-related genes such as <em>acn-1</em> and <em>daf-2</em> while simultaneously upregulating the longevity-promoting gene <em>daf-16</em>. Additionally, β-sitosterol induced notable metabolic changes, including elevated levels of oleic acid, and influenced developmental processes by modulating the <em>mir-61-5p/col-19</em> signalling axis. The compound also affected locomotory behaviour by engaging the serotonin signalling pathway through genes such as <em>tph-1, kpc-1,</em> and <em>rho-1</em>. Furthermore, β-sitosterol enhanced innate immunity by increasing the expression of antimicrobial peptide genes. Computational analyses suggested that β-sitosterol possesses favorable drug-like properties, reinforcing its potential as a therapeutic agent. Our findings highlight the beneficial effects of β-sitosterol, and its promise as a natural compound for promoting both longevity and healthspan in model organisms through proteomics and metabolomics approaches.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130899"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793199","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":"NPR3 promotes colorectal cancer cell proliferation, migration, invasion, and chemotherapy resistance","authors":"Wensheng Chen ,&nbsp;Qingshui Wang ,&nbsp;Shuyuan Li","doi":"10.1016/j.bbagen.2025.130895","DOIUrl":"10.1016/j.bbagen.2025.130895","url":null,"abstract":"<div><h3>Background</h3><div>Lymph node metastasis is a critical prognostic factor in colorectal cancer (CRC). Identifying key genes associated with metastasis can improve risk stratification and treatment strategies. This study aimed to identify a gene signature related to lymph node metastasis and investigate the role of NPR3.</div></div><div><h3>Methods</h3><div>We analyzed the GSE878211 dataset to identify differentially expressed genes in CRC tissues with and without lymph node metastasis. A lymph node metastasis-related gene signature (LNMRGS) was constructed using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The correlation between LNMRGS and clinical indicators, immune microenvironment, and signaling pathways was analyzed. The role of NPR3 was further investigated through in vitro and in vivo experiments.</div></div><div><h3>Results</h3><div>We identified 110 upregulated and 58 downregulated genes in CRC tissues with lymph node metastasis. The LNMRGS, consisting of Integrin Subunit Beta 3 (ITGB3), IQ Motif Containing with AAA Domain 1 (IQCA1), Angiopoietin-Like 4 (ANGPTL4), and Natriuretic Peptide Receptor 3 (NPR3), predicted overall survival in multiple datasets. High LNMRGS was associated with female sex, tumor recurrence, lymph node metastasis, distant metastasis, and KRAS mutations. NPR3 knockdown inhibited proliferation, migration, and invasion of CRC cells in vitro and in vivo, and reduced chemoresistance to 5-fluorouracil (5-FU) and oxaliplatin.</div></div><div><h3>Conclusion</h3><div>The LNMRGS is a robust prognostic signature for CRC. NPR3 plays a key role in metastatic progression and chemoresistance, suggesting it as a potential therapeutic target.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130895"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740625","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":"Development of benzoxazole-2-yl-guanidine based Cu (II), Co (II), and Ni (II) complexes: Structural features, physicochemical aspects underpinning their pharmaceutical potential supported with theoretical approaches","authors":"Ahmed M. Abu-Dief ,&nbsp;Samar B. Mohamed ,&nbsp;Mehran Feizi-Dehnayebi ,&nbsp;Inam Omar ,&nbsp;Manara A. Ayoub ,&nbsp;Maher Fathalla ,&nbsp;Mahmoud Abd El Aleem Ali Ali El-Remaily","doi":"10.1016/j.bbagen.2025.130893","DOIUrl":"10.1016/j.bbagen.2025.130893","url":null,"abstract":"<div><div>In this study, novel bioactive metal complexes of Cu (II), Co (II), and Ni (II) were synthesized using a guanidine-based ligand, 1,3-benzoxazole-2-yl-guanidine (L). The resulting coordination compounds [Cu(L)(CH₃COO)₂(H₂O)]·2H₂O, [Co(L)(NO₃)₂(H₂O)]·3H₂O, and [Ni(L)(NO₃)₂(H₂O)]·H₂O were comprehensively characterized using a range of physicochemical and spectroscopic techniques, including UV–visible spectrophotometry, FT-IR spectroscopy, elemental analysis, molar conductance, MS analysis, TGA, and magnetic measurements. The collected data support the formation of octahedral geometries around the metal centers, highlighting the ligand's flexible coordination behavior. Density functional theory (DFT) calculations were employed to optimize the molecular structures and support the experimental findings. Solution characterization established stoichiometric relationships, equilibrium constants, and pH-dependent properties, indicating their robustness in aqueous environments. The biological potential of the synthesized compounds was further evaluated through in vitro cytotoxicity assays (MTT) against HepG2 (liver), MCF-7 (breast), and HCT-116 (colon) cancer cell lines. Among the tested compounds, the Cu (II)-L complex exhibited the most pronounced antiproliferative activity, particularly against MCF-7 cells. Antioxidant capacity, assessed via DPPH radical scavenging assay, confirmed the strong free-radical neutralizing potential of the metal chelates. Antimicrobial investigations demonstrated broad-spectrum activity against various pathogenic strains, including <em>S. marcescens</em>, <em>M. luteus</em>, <em>E. coli</em>, <em>C. albicans, A. flavus</em>, and <em>F. oxysporum</em>. Notably, the copper complex exhibited significant antibacterial activity against <em>M. luteus</em> and potent antifungal effects against <em>F.oxysporum</em>. These effects highlight the therapeutic promise of guanidine-derived metal chelates as multifunctional agents with potential applications in anticancer, antioxidant, and antimicrobial therapies.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130893"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686563","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":"Cavin-3 promotes TNF expression via the MAPK signaling pathway in lung squamous cell carcinoma","authors":"Xiaoyan Xu ,&nbsp;Yonghong Nie ,&nbsp;Jiatuo Xu ,&nbsp;Rilei Jiang","doi":"10.1016/j.bbagen.2025.130892","DOIUrl":"10.1016/j.bbagen.2025.130892","url":null,"abstract":"<div><div>Cavin family proteins alter the invasiveness of tumor cells. However, research on the pathogenesis of Cavins in tumors is lacking. To address this knowledge-gap, we conducted a systematic analysis about the mechanism of action of Cavins in cancer. We evaluated the diagnostic value of Cavin-3 and its potential as a new therapeutic target for lung squamous cell carcinoma (LUSC). Bioinformatic analysis showed that Cavin-3 can inhibit LUSC tumor cells by regulating the expression of EREG and IL1A, thereby activating the MAPK pathway to promote the release of tumor necrosis factor (TNF) and other inflammatory factors. Moreover, in vitro experiments have shown that Cavin-3 may promote the expression of inflammatory factors by regulating the MAPK signaling pathway, thereby killing tumor cells and inhibiting tumor proliferation.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130892"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628483","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":"Trimethylamine N-oxide participates in human diseases by causing endoplasmic reticulum stress","authors":"Kritika Kumari ,&nbsp;Anuja Arora ,&nbsp;Nalini Natarajan ,&nbsp;Nasim Akhtar Ansari ,&nbsp;Laishram Rajendrakumar Singh","doi":"10.1016/j.bbagen.2025.130900","DOIUrl":"10.1016/j.bbagen.2025.130900","url":null,"abstract":"<div><div>The gut metabolite trimethylamine N-oxide (TMAO) is found to be elevated at high levels not only in the serum but also in the cerebrospinal fluid of humans. Elevated TMAO levels are associated with several human diseases, including cardiovascular complications, cognitive impairment, acute pancreatitis, cancer, and chronic kidney disease. Research on TMAO has also received significant attention due to its association with sudden cardiac arrest. Therefore, understanding the common molecular insight into the association of TMAO with these diseases has been an important intellectual curiosity. Although inflammation and oxidative stress are commonly regarded as hallmarks of TMAO-induced pathology, recent advances have further opened up a new dimension of its role in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). In the present manuscript, we attempted to present a novel mechanism wherein TMAO-UPR axis may underlie the pathogenesis of various human diseases by influencing specific signaling molecules (FOXO1, CREB, TLR4, SIRT1 and mTOR). These studies highlight strategies aimed at targeting TMAO-UPR axis could be promising for the therapeutic intervention of diseases caused by elevated TMAO.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130900"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846352","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":"Exploring the role of CCT7 in prognosis, cell cycle regulation, and immune microenvironment remodeling of lung adenocarcinoma based on multi-omics datasets and functional experiments","authors":"Lie Deng,&nbsp;JinHui Ruan,&nbsp;YunYan Li","doi":"10.1016/j.bbagen.2025.130896","DOIUrl":"10.1016/j.bbagen.2025.130896","url":null,"abstract":"<div><h3>Background</h3><div>Lung adenocarcinoma (LUAD) represents one of the most prevalent and lethal malignancies, accounting for a significant proportion of cancer-associated deaths worldwide. The persistently unfavorable clinical outcomes associated with this disease highlight the critical demand for identifying innovative molecular markers and developing targeted therapeutic interventions. The chaperonin-containing TCP-1 subunit 7 (CCT7) has been implicated in carcinogenesis across malignancies, but its specific role in LUAD pathogenesis and clinical utility remains poorly defined.</div></div><div><h3>Methods</h3><div>We evaluated CCT7 expression in LUAD using TCGA, GSE118370, CPTAC, and HPA datasets, correlating it with clinicopathological features and survival outcomes. Functional assays (cell cycle analysis, proliferation, colony formation) in A549/H1229 cells, single-cell RNA sequencing, miRNA regulatory studies, and drug sensitivity analyses (GDSC/CTRP) were performed to explore its mechanisms and clinical potential.</div></div><div><h3>Results</h3><div>CCT7 was significantly upregulated in LUAD at both mRNA and protein levels, associating with advanced pathological stages, lymph node metastasis, and poor survival (AUC &gt; 0.5 for 1-, 3-, and 5-year outcomes). It promoted LUAD proliferation via the FOXM1-POLE2 pathway, with knockdown inducing M-phase arrest. CCT7 shaped an immunosuppressive tumor microenvironment (reduced CD8+ T cells, elevated Th2 cells) and enhanced crosstalk between tumor cells and stromal/immune populations. Hsa-miR-145-5p negatively regulated CCT7. High CCT7 correlated with increased tumor mutational burden and sensitivity to FK866/Vorinostat, but resistance to Erlotinib.</div></div><div><h3>Conclusion</h3><div>CCT7 acts as an independent prognostic biomarker in LUAD, driving progression through cell cycle regulation, microenvironment remodeling, and immune modulation. It holds promise as a therapeutic target and guide for personalized LUAD treatment.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130896"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809193","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":"Non-equilibrium thermodynamics of cancer: Entropy dynamics and metastatic growth","authors":"Krzysztof W. Fornalski","doi":"10.1016/j.bbagen.2025.130898","DOIUrl":"10.1016/j.bbagen.2025.130898","url":null,"abstract":"<div><div>Cancer is a complex dissipative system operating far from equilibrium, characterized by increased entropy production compared to normal tissues. Traditional thermodynamic approaches often fail to capture its full dynamics. In this study, we apply non-equilibrium stochastic thermodynamics to analyze different stages of carcinogenesis: neoplastic transformation (using the Avrami–Dobrzyński approach), tumor growth (described by the Gompertz model), and metastasis, in relation to tumor entropy and self-organization. Our results reveal a relationship between entropy production and tumor expansion rate, indicating that cellular reproduction enhances entropy generation. We also examine the information entropy of <em>hepatocellular carcinoma</em> cells. Furthermore, we demonstrate that restricting external energy intake does not halt tumor progression, underscoring the resilience of cancer as an autonomous physical system. These findings highlight the thermodynamic nature of cancer and suggest that metastasis is an inevitable consequence of entropy-driven evolution.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 2","pages":"Article 130898"},"PeriodicalIF":2.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780065","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":"Elevated cyclic hydrostatic pressure enhances the transfection activity of lipoplexes by activating clathrin-mediated endocytosis","authors":"Weichen Zhan ,&nbsp;Xiaowei Ding ,&nbsp;Zhongrui Cui ,&nbsp;Yizhuo Wu ,&nbsp;Yiwen Gu ,&nbsp;Hanxiao Cheng ,&nbsp;Xinxin Ge ,&nbsp;Yun Wang ,&nbsp;Jiangyun Luo ,&nbsp;Bing Xiao","doi":"10.1016/j.bbagen.2025.130878","DOIUrl":"10.1016/j.bbagen.2025.130878","url":null,"abstract":"<div><div>Despite significant advancements in liposome-mediated transfection technology over the past decades, achieving optimal transfection efficiency with lipoplex remains challenging in certain primary cells, such as vascular smooth muscle cells, endothelial cells, and suspension cells. Here, we present an innovative approach to significantly enhance Lipofectamine-based transient transfection efficiency in hard-to-transfect cells by applying elevated cyclic hydrostatic pressure (CHP). The plasmids encoding the enhanced green fluorescent protein (EGFP) were transfected using Lipofectamine 3000 reagent, and the transfection efficiency was evaluated by Western blot or flow cytometry. Our results demonstrate that CHP (0.0083 Hz, 0–100 mmHg) significantly enhanced the transfection efficiency of lipoplex in primary human aortic smooth muscle cells (HASMCs) and other difficult-to-transfect cell types. Mechanistic studies revealed that the enhancement of liposome-mediated transfection by CHP was dependent on the activation of clathrin-dependent endocytic pathways. Importantly, this mechanical stimulation did not affect the proliferative or migratory capacities of HASMCs, despite the identification of significantly modulated proteins (5.8 % of the total proteome) by proteomic analysis. This study establishes a novel, safe strategy to enhance lipoplex-mediated nucleic acid delivery in challenging-to-transfect cell types.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130878"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437017","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":"The role of ATM in sodium butyrate-mediated inhibition of macrophage polarization","authors":"Yan-Yan Guo,&nbsp;Xia-Nan Chu,&nbsp;Pei-Hua Wang,&nbsp;Ya-Qian Li,&nbsp;Li Xing","doi":"10.1016/j.bbagen.2025.130881","DOIUrl":"10.1016/j.bbagen.2025.130881","url":null,"abstract":"<div><div>DNA damage response (DDR) signaling not only maintains genomic integrity but also plays a role in the activation of immune cells, including macrophages. In response to the stimuli, macrophages can be polarized into a proinflammatory phenotype, M1. In the monocytoid THP-1 cell-derived macrophage model, sodium butyrate was found to inhibit the expression of M1 biomarkers TNF-α, IL-6, IL-1β, and CXCL10, and downregulate DDR-associated proteins, including the apical Ataxia-Telangiectasia mutated protein kinase (ATM). However, siRNA-mediated knockdown of ATM did not reduce the expression of M1 biomarkers, but still downregulated the expression of DDR-associated proteins such as RAD50, p53, CHK1, NBS1, and γH2AX. Moreover, ATM knockdown modulated the expression of innate immunity regulatory genes, including sialic acid binding immunoglobulin type lectins 14 (Siglec14), Siglec15, signaling lymphocyte activation molecule family 1 (Siamf1), Siamf7, and guanylate binding protein 2 in response to the infection of <em>Mycobacterium tuberculosis</em> H37Ra. The results suggest that ATM may serve as a regulator to couple the DDR and innate immune response of macrophages, but barely contributes to the sodium butyrate-mediated inhibition of certain M1 biomarkers.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130881"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457084","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}