Biochimica et biophysica acta. Molecular cell research最新文献_第5页

Prevotella copri leads to colonic barrier dysfunction via the succinate receptor 1-FoxM1-IL-6 axis copri普雷沃氏菌通过琥珀酸受体1-FoxM1-IL-6轴导致结肠屏障功能障碍。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-03-01 Epub Date: 2025-12-30 DOI: 10.1016/j.bbamcr.2025.120099

Rui Li , Shuang Liu , Haiyan Zhang , Xinglin Huang , Wenchu Qian , Daobin Han , Fang Wang , Zhonghui Feng , Tongtong Zhang , Hai Lin , Haifang Li

{"title":"Prevotella copri leads to colonic barrier dysfunction via the succinate receptor 1-FoxM1-IL-6 axis","authors":"Rui Li , Shuang Liu , Haiyan Zhang , Xinglin Huang , Wenchu Qian , Daobin Han , Fang Wang , Zhonghui Feng , Tongtong Zhang , Hai Lin , Haifang Li","doi":"10.1016/j.bbamcr.2025.120099","DOIUrl":"10.1016/j.bbamcr.2025.120099","url":null,"abstract":"<div><div><em>Prevotella copri</em>, a key commensal bacterium in the human gut microbiome, exhibits both positive and negative abundance correlations with various disorders. Although multiple studies have suggested an association between <em>P. copri</em> and intestinal pathologies, the mechanistic basis remains elusive. In this study, we examined <em>P. copri</em>'s effects on colonic physiology in healthy mice, revealing its capacity to compromise intestinal barrier integrity. This was demonstrated through downregulation of colonic tight junction proteins (Occludin and ZO-1) and elevated serum levels of gut permeability markers (LPS and D-LA). We identified succinate as the primary microbial metabolite mediating <em>P. copri</em>'s barrier-disrupting effects, with succinate receptor 1 (SUCNR1) being essential for this pathological process. Notably, both <em>P. copri</em> colonization and succinate administration activated the IL-6-STAT3 signaling pathway, leading to transcriptional suppression of the tight junction-related gene, <em>Occludin</em>. Through mechanistic studies, we identified Forkhead box M1 (FoxM1) as a crucial transcription factor regulating <em>P. copri</em>- or succinate-induced <em>Il-6</em> expression. Clinical relevance was established through human cohort analyses showing significant positive correlations between fecal succinate levels and plasma markers of gut permeability. These findings elucidate a novel mechanistic pathway through which <em>P. copri</em> impairs colonic function, suggesting therapeutic potential in colitis through strategies targeting either <em>P. copri</em> abundance or microbial succinate production.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 3","pages":"Article 120099"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SPRED2 controls the severity of cisplatin-induced acute kidney injury by inhibiting ERK activation and TNFα production in mice SPRED2通过抑制小鼠ERK活化和TNFα产生来控制顺铂诱导的急性肾损伤的严重程度

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-02-01 Epub Date: 2025-11-30 DOI: 10.1016/j.bbamcr.2025.120091

Xu Yang , Jiali He , Tong Gao , Masayoshi Fujisawa , Toshiaki Ohara , Steven L. Kunkel , Teizo Yoshimura , Akihiro Matsukawa

{"title":"SPRED2 controls the severity of cisplatin-induced acute kidney injury by inhibiting ERK activation and TNFα production in mice","authors":"Xu Yang , Jiali He , Tong Gao , Masayoshi Fujisawa , Toshiaki Ohara , Steven L. Kunkel , Teizo Yoshimura , Akihiro Matsukawa","doi":"10.1016/j.bbamcr.2025.120091","DOIUrl":"10.1016/j.bbamcr.2025.120091","url":null,"abstract":"<div><div>Cisplatin is an effective chemotherapeutic agent used to treat solid tumors, but its clinical use is limited by acute kidney injury (AKI), in which ERK signaling plays a crucial role. Here, we investigated whether Sprouty-related EVH1 domain-containing protein 2 (SPRED2), an endogenous inhibitor of the Ras/Raf/ERK pathway, protects against cisplatin-induced AKI. <em>Spred2</em><sup><em>−/−</em></sup> mice showed more severe renal injury and stronger ERK activation than wild-type (WT) mice, whereas pretreatment with the MEK inhibitor U0126 markedly attenuated the injury. In HK-2 cells (proximal tubular cells), SPRED2 knockdown enhanced cisplatin-induced apoptosis and caspase-3 activation, accompanied by decreased Bcl-2 expression. <em>Spred2</em><sup><em>−/−</em></sup> kidneys displayed increased macrophage infiltration and elevated <em>Tnfα</em>, <em>Il1b</em>, and <em>Ccl2</em> expression. Neutralization of TNFα with anti-TNFα antibody ameliorated renal injury and reduced the levels of <em>Il1b</em> and <em>Ccl2</em> mRNA in <em>Spred2</em><sup><em>−/−</em></sup> mice. In vitro, TNFα slightly decreased the viability of control and SPRED2 knockdown HK-2 cells without cisplatin treatment, but the decreased viability was augmented in SPRED2 knockdown cells by cisplatin. Immunohistochemistry revealed that macrophages were the predominant TNFα-positive cell population. Bone marrow–derived macrophages from <em>Spred2</em><sup><em>−/−</em></sup> mice produced higher levels of TNFα in response to cisplatin compared with control cells, and this increase was markedly suppressed by U0126.</div><div>These findings indicate that endogenous SPRED2 protects kidneys from cisplatin-induced AKI by limiting ERK activation, tubular apoptosis, and TNFα-mediated inflammation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 2","pages":"Article 120091"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145658682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing the involvement of tumor-secreted factors in the inhibition of muscle differentiation 评估肿瘤分泌因子在肌肉分化抑制中的作用

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.bbamcr.2025.120093

Miranda van der Ende , Xiaolin Li , Mieke Poland , Fleur Jansen , Jocelijn Meijerink , Jaap Keijer , Renger F. Witkamp , Sander Grefte , Klaske van Norren

{"title":"Assessing the involvement of tumor-secreted factors in the inhibition of muscle differentiation","authors":"Miranda van der Ende , Xiaolin Li , Mieke Poland , Fleur Jansen , Jocelijn Meijerink , Jaap Keijer , Renger F. Witkamp , Sander Grefte , Klaske van Norren","doi":"10.1016/j.bbamcr.2025.120093","DOIUrl":"10.1016/j.bbamcr.2025.120093","url":null,"abstract":"<div><div>Cancer cachexia is a multifactorial syndrome characterized by involuntary and pathological weight loss, predominantly caused by muscle wasting. While tumors can elicit detrimental effects on skeletal muscle function, the contribution of specific tumor-derived mediators remains elusive. To explore this, we investigated the impact of conditioned media (CM) from four cachexia-inducing tumor cell lines (KPC, 4662, LLC, and C26) on muscle differentiation using C2C12 cells. Creatine kinase (CK) activity was measured as an indicator of muscle wasting, and global gene expression changes in C2C12 cells were analyzed via RNA sequencing. Cytokine profiling of the CM identified 111 immune factors, and mimic combinations of the most abundant cytokines from KPC CM were tested for their effects on CK activity. Additionally, the involvement of tumor-derived PGE2 was assessed via CRISPR/Cas9-mediated knockout of the <em>Ptgs2</em> gene in KPC cells. CM from all tumor cell lines significantly reduced CK activity in C2C12 cells, consistent with downregulation of <em>CKm</em> gene expression. Global gene expression profiles revealed upregulation of immune-related pathways in C2C12 cells exposed to KPC CM. However, mixtures of the 14 most abundant cytokines in CM had minimal effects on CK activity, and tumor-derived PGE2 showed no significant effect on CK activity or muscle cell differentiation. These findings suggest that the observed muscle-wasting effects of cachexia-inducing tumor cells cannot be replicated by the most abundant cytokines present in CM alone, highlighting the need for further research to identify the key tumor-derived factors responsible for cancer-induced muscle wasting.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 2","pages":"Article 120093"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic reprogramming is implicated in the differential response of the CAL-1 plasmacytoid dendritic cell line to autophagy inhibitors 代谢重编程涉及CAL-1浆细胞样树突状细胞系对自噬抑制剂的差异反应。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-02-01 Epub Date: 2025-11-27 DOI: 10.1016/j.bbamcr.2025.120090

Carlota Ramalhinho , Paulo Antas , Philippe Pierre , Iola F. Duarte , Catarina R. Almeida

{"title":"Metabolic reprogramming is implicated in the differential response of the CAL-1 plasmacytoid dendritic cell line to autophagy inhibitors","authors":"Carlota Ramalhinho , Paulo Antas , Philippe Pierre , Iola F. Duarte , Catarina R. Almeida","doi":"10.1016/j.bbamcr.2025.120090","DOIUrl":"10.1016/j.bbamcr.2025.120090","url":null,"abstract":"<div><div>Plasmacytoid dendritic cells (pDCs) produce large amounts of type I Interferons (IFN) and pro-inflammatory cytokines, playing crucial roles in antiviral and anticancer immunity as well as in autoimmune diseases. Understanding the mechanisms that regulate pDC function is therefore essential. Autophagy, a process responsible for recycling intracellular components, influences cellular metabolism and modulates immune responses. Here, we used the human CAL-1 pDC cell line, a validated model for primary pDCs, to investigate the functional impact of autophagy inhibition and the contribution of metabolism to these effects. CAL-1 cells were treated with two autophagy inhibitors, Spautin-1 and VPS34-IN1, and cytokine production was assessed by RT-qPCR and ELISA, while cellular metabolism was analysed by untargeted metabolomics of cell extracts and of medium supernatants. VPS34-IN1, but not Spautin-1, induced robust expression of IFN-β and TNF-α. The two inhibitors also elicited distinct metabolic responses: Spautin-1 enhanced glycolysis, promoted an anabolic phenotype with increased utilization of amino acids, and upregulated mTOR signaling. In contrast, VPS34-IN1 decreased glycolysis, increased intracellular amino acids, reduced TCA intermediates, and induced energy stress, reflected by an increased AMP/(ADP + ATP) ratio and decreased NAD<sup>+</sup>. These changes were consistent with AMPK activation, and pharmacological inhibition of AMPK with dorsomorphin (compound C) abolished cytokine production in VPS34-IN1-treated cells. Together, these results indicate that differential cytokine responses to autophagy inhibition are driven primarily by metabolic rewiring rather than autophagic flux per se, highlighting the interplay between metabolism, mitochondrial ROS, and signaling pathways in pDC activation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 2","pages":"Article 120090"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “A fluorescent protein C-terminal fusion knock-in is functional with TRPA1 but not TRPC5” [Biochim. Biophys. Acta Mol. Cell Res. 1872(2) (2025) 119887] “一种荧光蛋白c端融合敲入对TRPA1起作用，但对TRPC5不起作用”的更正[biochem]。Biophys。分子细胞学报，1872(2)(2025)[19887]。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-02-01 Epub Date: 2025-08-15 DOI: 10.1016/j.bbamcr.2025.120042

Aaron Tragl , Alexandra Ptakova , Viktor Sinica , Rathej Meerupally , Christine König , Carolina Roza , Ivan Barvík , Viktorie Vlachova , Katharina Zimmermann

引用次数: 0

Corrigendum to “Protein synthesis inhibition promotes nitric oxide generation and activation of CGKII-dependent downstream signaling pathways in the retina” [Biochim. Biophys. Acta (BBA) Mol. Cell Res. 1867 (2020) 118732 10.1016/j.bbamcr.2020.118732] “蛋白质合成抑制促进一氧化氮的产生和视网膜中cgkii依赖的下游信号通路的激活”[biochem]的更正。Biophys。[j].中国生物医学工程学报，2016,32(1):1 - 2。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-02-01 Epub Date: 2025-09-01 DOI: 10.1016/j.bbamcr.2025.120050

Marcelo Cossenza , Renato Socodato , Telmo A. Mejía-García , Ivan Domith , Camila C. Portugal , Luis F.H. Gladulich , Aline T. Duarte-Silva , Latika Khatri , Shannon Antoine , Franz Hofmann , Edward B. Ziff , Roberto Paes-de-Carvalho

引用次数: 0

Corrigendum to “Inhibition of autophagy sensitises cells to hydrogen peroxide-induced apoptosis: Protective effect of mild thermotolerance acquired at 40 °C” [Biochim. Biophys. Acta Mol. Cell Res. (2016) volume 1863(12) 3050-3064 / PMID: 27666506] “抑制自噬使细胞对过氧化氢诱导的凋亡敏感：在40°C下获得的轻度耐热性的保护作用”[biochem]的更正。Biophys。Acta Mol Cell Res. (2016) volume 1863(12) 3050-3064 / PMID: 27666506]。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-02-01 Epub Date: 2025-09-19 DOI: 10.1016/j.bbamcr.2025.120061

M. Redza-Dutordoir, S. Kassis, H. Ve, M. Grondin, D.A. Averill-Bates

引用次数: 0

Sustained Galiellalactone treatment breaks the metastatic resilience of BRAF-inhibitor-resistant melanoma cells 持续的盖ellalactone治疗打破braf抑制剂抵抗黑色素瘤细胞的转移弹性

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-02-01 Epub Date: 2025-12-10 DOI: 10.1016/j.bbamcr.2025.120096

Sujoy Bhowmik, Saumya Ranjan Badajena , Satyajit Laxman Murkute , Dumarapu Bhagyalaxmi, Purusottam Mohapatra

{"title":"Sustained Galiellalactone treatment breaks the metastatic resilience of BRAF-inhibitor-resistant melanoma cells","authors":"Sujoy Bhowmik, Saumya Ranjan Badajena , Satyajit Laxman Murkute , Dumarapu Bhagyalaxmi, Purusottam Mohapatra","doi":"10.1016/j.bbamcr.2025.120096","DOIUrl":"10.1016/j.bbamcr.2025.120096","url":null,"abstract":"<div><div>STAT3 hyperactivation in metastatic and therapy-resistant melanoma drives tumorigenesis and immunotherapy resistance by promoting tumor-stromal interactions, making its inhibition a crucial therapeutic strategy. Interestingly, synthetic STAT3 inhibitors could not manage to enter clinical trials due to their short half-lives, poor bioavailability and non-specific effects. Here, we have shown that Galiellalactone, a natural, irreversible STAT3 inhibitor, blocks IL-6 and WNT5A-mediated STAT3 Phosphorylation and migration in BRAF-inhibitor (BRAFi)-sensitive melanoma cells. Galiellalactone treatment leads to prolonged STAT3 inhibition, which obstructs both metastatic functions and secretome-mediated paracrine interactions in both BRAFi-sensitive and resistant melanoma cells, <em>via</em> the reduction of MCAM and N-cadherin protein expression. Altogether, our findings support that Galiellalactone is a potential inhibitor that could block the metastatic function of drug-resistant melanoma cells and also obstruct the possible paracrine activation of STAT3 conferred by stromal cells present in the tumor microenvironment.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 2","pages":"Article 120096"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Activation of ER stress and apoptosis by hydrogen peroxide in HeLa cells: Protective role of mild heat preconditioning at 40 °C” [Biochim. Biophys. Acta Mol. Cell Res., 1813 (2011) 1987–1999. / PMID: 21875624] “过氧化氢在HeLa细胞中内质网应激和凋亡的激活：40°C轻度热预处理的保护作用”的更正[biochem]。Biophys。分子细胞学报，1813(2011)1987-1999。/ pmid: 21875624]。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-02-01 Epub Date: 2025-11-12 DOI: 10.1016/j.bbamcr.2025.120084

Pragathi Pallepati, Diana A. Averill-Bates

引用次数: 0

Structural diversity of full-length human αvβ3 integrin revealed by cryo-EM 低温电镜分析人αvβ3整联素的结构多样性。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2026-02-01 Epub Date: 2025-11-29 DOI: 10.1016/j.bbamcr.2025.120089

Cang Wu , Yuanzhu Gao , Weiyan Wang , Zhoufang Li , Qing Shu , Xi Zhang

{"title":"Structural diversity of full-length human αvβ3 integrin revealed by cryo-EM","authors":"Cang Wu , Yuanzhu Gao , Weiyan Wang , Zhoufang Li , Qing Shu , Xi Zhang","doi":"10.1016/j.bbamcr.2025.120089","DOIUrl":"10.1016/j.bbamcr.2025.120089","url":null,"abstract":"<div><div>Integrins are essential transmembrane receptors that orchestrate cell adhesion, migration, and survival, and have emerged as promising therapeutic targets for cancer, fibrosis, and autoimmune diseases. However, most integrin-targeted drugs have failed in clinical trials due to limited efficacy and unexpected off-target effects, reflecting an incomplete understanding of integrin conformational regulation. Here, we present a series of high-resolution cryo-EM structures of human integrin αvβ3 in both apo and ligand-bound states by collecting a large amount of data. Consequently, we resolved six conformations of integrin in the apo state, five of which were previously uncharacterized, along with five distinct ligand-bound states, thereby revealing a continuum of conformational transitions underlying integrin activation. Notably, CWHM-12 enables the simultaneous coexistence of integrin in closing and opening inhibited states, revealing a mechanism that differs fundamentally from that of conventional RGD peptide-based inhibitors. Then, our study provides a structural framework for understanding integrin activation diversity and lays the foundation for rational design of next-generation inhibitors with improved precision and reduced off-target effects.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 2","pages":"Article 120089"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0