Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"Anti-tumor response by targeting glucose metabolism and depletion of membrane cholesterol in breast cancer and melanoma cells","authors":"Himanshi Yaduvanshi,&nbsp;Bhavana Deshmukh,&nbsp;Abhijeet Singh,&nbsp;Shyamananda Singh Mayengbam,&nbsp;Manoj Kumar Bhat","doi":"10.1016/j.bbamcr.2025.120088","DOIUrl":"10.1016/j.bbamcr.2025.120088","url":null,"abstract":"<div><div>Enhanced lactate production and cholesterol accumulation in cancer cells are often correlated with poor prognosis and the development of resistance to therapies. This study investigates a unique dual-pronged approach for abrogating tumor development by combining methyl-β-cyclodextrin (MCD)-mediated cholesterol depletion with sodium oxamate (OXA)-induced inhibition of lactate dehydrogenase A.</div><div>The cytotoxic effects of MCD and OXA were validated by MTT and long-term colony formation assay. Cell cycle arrest and apoptosis were assessed via flow cytometry. The involvement of key signaling intermediates in proliferative pathways was evaluated by immunoblotting. The Seahorse analyzer was used to measure the real-time metabolic flux in mouse cancer cells. In vivo<em>,</em> studies and immunophenotyping were performed to investigate the impact of MCD+OXA treatment on tumor growth and immune cell infiltration in tumor and periphery organs. The results indicate that concurrent administration of a low-dose MCD and OXA elicited a synergistic cytotoxic effect and retarded tumor progression while being non-toxic to vital organs. Mechanistically, this combination downregulated ERK/AKT signaling, induced apoptosis, and suppressed cellular metabolism at the glycolysis/OXPHOS level, including ATP production. Interestingly, it promoted the infiltration of effector Th1 cells and B cells, while reducing the presence of PMN-MDSCs in the tumor microenvironment and peripheral organs. These findings suggest that the combination of MCD and OXA provides a dual-targeted approach by disrupting cholesterol as well as lactate metabolism and eliciting an anti-tumor immune response, leading to a reduction in the growth of tumor cells. This pre-clinical strategy demonstrates potential advantages over single-agent treatment, which warrants further investigations for its therapeutic implications.</div></div><div><h3>Summary blurb</h3><div>In pre-clinical investigations, co-targeting membrane cholesterol, and lactate dehydrogenase A with methyl-β-cyclodextrin and sodium oxamate inhibits cell growth and restricts breast cancer and melanoma tumor progression.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120088"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145547869","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}

{"title":"Basic leucine zipper ATF-like transcription factor (Batf) aggravates central sensitization in nitroglycerin-induced chronic migraine mouse model","authors":"Yanhong Liu ,&nbsp;Xiaoyu Tong","doi":"10.1016/j.bbamcr.2025.120078","DOIUrl":"10.1016/j.bbamcr.2025.120078","url":null,"abstract":"<div><div>Chronic migraine (CM) is a widespread neurological disorder with heterogeneous underlying causes. Basic leucine zipper ATF-like transcription factor (Batf) can amplify neuroinflammatory responses, but therapeutic strategies targeting Batf in CM remain unclear. Here, we investigated the role of Batf in a nitroglycerin (NTG)-induced CM mouse model and lipopolysaccharide (LPS)-induced BV-2 cells. Batf and Iba-1 expression were enhanced in the trigeminal nucleus caudalis (TNC) of NTG-induced mice. Batf knockdown mitigated NTG-induced central sensitization, decreased CGRP and c-Fos expression, and inhibited Iba-1, iNOS, IL-18, and IL-1β expression in TNC of NTG-induced mice. Furthermore, the NLRP3 inflammasome in TNC of NTG-induced mice was inhibited by Batf knockdown. Our results suggested that Batf knockdown attenuated central sensitization through mediating microglial activation via the NLRP3 inflammasome in the TNC of CM mice. Batf might be a candidate for migraine treatment.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120078"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145413205","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}

{"title":"NRAMP family in plants: Contribution to cadmium accumulation","authors":"Katarzyna Kozak ,&nbsp;Danuta Maria Antosiewicz","doi":"10.1016/j.bbamcr.2025.120056","DOIUrl":"10.1016/j.bbamcr.2025.120056","url":null,"abstract":"<div><div>The Natural Resistance Associated Macrophage Proteins (NRAMPs) are membrane-targeted transporters with low substrate specificity, that mediate the import (translocation to the cytoplasm) of metals, mainly essential nutrients, e.g. iron (Fe), manganese (Mn), zinc (Zn), cobalt (Co), copper (Cu) or nickel (Ni). Depending on the subcellular localisation, they contribute to either uptake or redistribution. Numerous studies have shown that NRAMP proteins also mediate the transport of non-essential toxic metals, and constitute the major pathway for the uptake of cadmium (Cd) in plants. Given the threat to living organisms from exposure to this toxic metal, which enters the food chain through edible plant parts, this review focuses on how different NRAMP proteins are involved in Cd uptake and accumulation. The issue was discussed concerning three categories of plants: (i) the model plant <em>Arabidopsis thaliana</em>; (ii) crop plants that are mainly used for food; (iii) plant species used for the phytoremediation of Cd-polluted environments, including hyperaccumulators. For the sake of clarity, this paper updates the structure, function and regulation of <em>NRAMP</em> genes and proteins, their phylogenetic relationships, and their substrates, filling a knowledge gap, and discussing these topics in light of new data. Furthermore, this review discusses the potential applications of <em>NRAMP</em> genes in plant biotechnology, such as generating low-Cd food and phytoremediation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120056"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008167","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}

{"title":"TRPV4 is involved in progesterone-mediated sexual dimorphism in mesenchymal stem cell functions and bio-mineralization","authors":"Nishant Kumar Dubey ,&nbsp;Satish Kumar ,&nbsp;Shamit Kumar ,&nbsp;Subham Mishra ,&nbsp;Nilesh Kumar Das ,&nbsp;Chandan Goswami","doi":"10.1016/j.bbamcr.2025.120066","DOIUrl":"10.1016/j.bbamcr.2025.120066","url":null,"abstract":"<div><div>The prevalence of bone disorders in female has been linked with imbalances in sex hormones, especially during pregnancy and menopause. Apart from regulation of transcription, recent reports suggest the involvement of various ion channels which can also be the molecular targets of an array of steroids (and steroid-like molecules). The differences in steroid responses between males and females also impose the need to understand the complexity of steroid actions. This current <em>in vitro</em> study has been carried out during the osteoblast differentiation (day 1 and day 12, early and late time points respectively) using MSCs-derived from male and female animals and in the presence of progesterone (P4) and/or TRPV4 modulators to explore the existence of sexual dimorphism at the cellular level if any and possible involvement of TRPV4 and P4 in it. Different subcellular parameters such as cytosolic Ca²⁺, mitochondrial potential, cytosolic- and mitochondrial-ROS and functional assays such as bio-mineralization (BM) were performed. All these results point out that P4 modulates TRPV4 both in the short-term and long-term, but differently in male and female-derived primary cells. It is observed that P4 can modulate TRPV4 in a long-term, both transcription-dependent and transcription-independent manner. Thus, the observed sexual dimorphism at the cultured cellular system is more prominent in the early time point which seems to be dampened, but still exists in the later time points. These findings may be relevant for bone disorders due to hormonal imbalance.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120066"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190774","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}

{"title":"Arabidopsis thaliana loss-of-function chloroplast tata mutants display an albino phenotype indicating a chloroplast-only function","authors":"Sarah Jessup ,&nbsp;Ruchira Sepali Mallawa Arachchi ,&nbsp;Chris Carrie","doi":"10.1016/j.bbamcr.2025.120068","DOIUrl":"10.1016/j.bbamcr.2025.120068","url":null,"abstract":"<div><div>A functional mitochondrial Tat (mtTat) pathway has been confirmed in plants, but the existence or need for a TatA subunit remains unanswered.</div><div>Two competing hypotheses have suggested that either plant mitochondria contain an unusual Tat pathway with no TatA contribution, or the chloroplast TatA (cpTatA) is dually targeted to chloroplasts and mitochondria.</div><div><em>Arabidopsis thaliana cptata</em> loss-of-function mutants display an albino phenotype consistent with a dysfunctional chloroplast Tat pathway with no quantitative impact on mitochondrial complex III biogenesis, reiterating a chloroplast-specific role of cpTatA.</div><div>While these findings reject the dual-targeting hypothesis, the roles and components of the plant mitochondrial Tat pathway are yet to be fully elucidated.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120068"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257088","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}

{"title":"Escitalopram disrupts PDK1–Akt signaling in B cells through a structure-dependent mechanism independent of SERT","authors":"Yu-Lun Tseng ,&nbsp;Meng-Ling Chiang","doi":"10.1016/j.bbamcr.2025.120086","DOIUrl":"10.1016/j.bbamcr.2025.120086","url":null,"abstract":"<div><div>The PI3K–Akt pathway is a central regulator of survival and growth signals across receptor systems, controlled at the membrane-proximal PDK1–Akt signaling node. Although selective serotonin reuptake inhibitors (SSRIs) primarily target the serotonin transporter (SERT), evidence suggests additional effects on intracellular signaling. Escitalopram, a widely used SSRI, was previously shown to inhibit Syk phosphorylation in platelets, raising the possibility of SERT-independent effects on kinase cascades. Here, we investigated whether escitalopram and related compounds interfere with PI3K–Akt signaling in Ramos B lymphoma cells stimulated through the B cell receptor (BCR). Escitalopram and its enantiomer R-citalopram selectively reduced phosphorylation of Akt and its downstream effector FoxO1 while sparing upstream Syk and parallel ERK and PLC–PKC pathways. To localize the site of interference, we combined analyses of PDK1-dependent targets with a PTEN-inhibition model. Escitalopram suppressed PLK1 and S6K1 phosphorylation without altering mTORC2 autophosphorylation, and it also reduced H₂O₂-induced Akt phosphorylation. These complementary results point to a downstream site of interference at the level of PDK1–Akt complex formation, beyond PI3K and PIP3 availability. By contrast, the structurally related analog <em>N</em>-methyl-citalopram showed no effect, reinforcing a structure-dependent mechanism of interference with PDK1–Akt signaling. Functionally, escitalopram enhanced apoptosis in BCR-stimulated cells. Similar inhibition under insulin and SDF-1 stimulation indicates a generalized, receptor-independent effect. These findings reveal a noncanonical, SERT-independent mechanism by which escitalopram disrupts PDK1–Akt activation, with potential relevance to the broader intracellular effects of SSRI treatment.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120086"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494531","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}

{"title":"Developmental spatiotemporal switching of the germline-specific subunits of heterodimeric NAC protein in Drosophila melanogaster","authors":"Elena A. Mikhaleva ,&nbsp;Natalia V. Akulenko ,&nbsp;Oxana M. Olenkina ,&nbsp;Yuri A. Abramov ,&nbsp;Sergey A. Lavrov ,&nbsp;Thoomas A. Leinsoo ,&nbsp;Sofia V. Marfina ,&nbsp;Georgij Arapidi ,&nbsp;Victoria Shender ,&nbsp;Sergei S. Ryazansky ,&nbsp;Galina L. Kogan ,&nbsp;Vladimir A. Gvozdev","doi":"10.1016/j.bbamcr.2025.120085","DOIUrl":"10.1016/j.bbamcr.2025.120085","url":null,"abstract":"<div><div>The ribosome-associated αβ heterodimeric ubiquitously expressed NAC protein is involved in protein homeostasis in eukaryotes. We previously reported that the germline-specific α and β subunits (gNACαβ) differ from ubiquitously expressed paralogs by the presence of extended intrinsically disordered regions. The embryonic precursors of the germline (pole cells) express both α and β gNAC subunits. CRISPR/Cas9-mediated knockout of the gNAC α- subunit gene resulted in the death of pole cells progenitors, implicating gNAC as an essential component of the germ plasm responsible for the germline development. Immunofluorescence detection was used to track changes in the expression of α- and β-subunits of gNAC during development. The bright fluorescence of the α-subunit in the germarium strongly decreases during oocyte specification and is replaced by the onset of increased β-subunit fluorescence, especially in the posterior part of mature oocytes, in the germ plasm region, where NACα-subunit fluorescent signal is absent. The visualized switches of gNAC subunits presence, as well as detection of separate cytoplasmic fluorescent puncta for α and β gNAC subunits in a germline cells (elongating spermatids in testis or embryonic pole cells), are explained by transient formation the hybrid NAC heterodimers composed of α or β germline subunit and a ubiquitous partner. The formation of hybrids, demonstrated by mass spectrometry analysis in testes, indicates a programed spatiotemporal functioning of both the ubiquitous and germline-specific NAC paralogs to support the germline-specific proteostasis.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120085"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494456","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}

{"title":"Loss of Sugen Kinase 495 in macrophages alleviates chronic colitis by improving mitochondrial stress","authors":"Jikai He ,&nbsp;Yuanmei Lou ,&nbsp;Pingan Yao ,&nbsp;Shiguang Yang ,&nbsp;Jinliang Dong ,&nbsp;Qifeng Yu","doi":"10.1016/j.bbamcr.2025.120072","DOIUrl":"10.1016/j.bbamcr.2025.120072","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD), highlighted by chronic intestinal inflammation, is an escalating global health concern. The pathogenesis of IBD is not fully understood, with DSS-induced chronic colitis in mice serving as a prevalent model, characterized by an increase in Ly6C^high macrophages—a signature of IBD. Sugen Kinase 495 (Sgk495), also known as serine/threonine kinase 40 (STK40), is known to influence cell differentiation, has an obscure role in mitochondrial in macrophage and its molecular mechanisms. Our research demonstrates that Sgk495 exacerbates chronic colitis in mice by disrupting colon structure and function and enhancing colonic pathology. The absence of Sgk495 in macrophage cells resulted in a reduction in the proportion of Ly6C^high macrophage. Mechanistically, Sgk495 silencing also improved mitochondrial stress by upregulated PINK1, Parkin, TOMM20 and DRP1, while reducing FOXO3a phosphorylation. Knockout of Sgk495 downregulates FOXO3a phosphorylation and improves mitochondrial stress, inhibits Ly6C^high macrophage polarization, and alleviates chronic colonic inflammation. Sgk495 may serve as a new potential therapeutic target for IBD.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120072"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145413215","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}

{"title":"Adipose-derived stem cells (ADSCs)-derived DKK1 promotes cutaneous wound healing by inducing M2 macrophage polarization via PI3K/AKT and JNK activation","authors":"Daiming Liu ,&nbsp;Ning Liu ,&nbsp;Xinxuan Liu ,&nbsp;Yi Liu ,&nbsp;Hongjia Zhang ,&nbsp;Zhuoqian Zhou ,&nbsp;Jiawang Zheng ,&nbsp;Yi Tian","doi":"10.1016/j.bbamcr.2025.120077","DOIUrl":"10.1016/j.bbamcr.2025.120077","url":null,"abstract":"<div><div>Wound healing requires the coordinated resolution of inflammation and tissue regeneration, whereby the role played by macrophage polarization is critical. This study investigates whether adipose-derived stem cells (ADSCs) promote wound repair through paracrine dickkopf-related protein 1 (DKK1) and explores their regulatory mechanism on macrophage polarization. In a murine full-thickness skin wound model, ADSCs treatment significantly enhanced re-epithelialization, collagen deposition, and Ki67 expression levels, while reducing local inflammatory cytokines and promoting M2 macrophage polarization. <em>In vitro</em>, ADSCs suppressed proinflammatory cytokines and induced M2 markers in LPS/IFN-γ-stimulated macrophages, an effect that was attenuated upon DKK1 knockdown. Mechanistically, DKK1 enhanced PI3K/AKT and JNK pathway activation both in macrophages and wound tissue. DKK1-deficient ADSCs showed a diminished ability to promote wound healing, reduce inflammation, and modulate macrophage phenotypes. These findings identify DKK1 as a key paracrine mediator of ADSCs-driven immunomodulation and tissue regeneration, thereby providing new insights into optimizing stem cell-based therapies for wound healing.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120077"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430363","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}

{"title":"Endothelial ANGPT2 impairs cardiomyocyte calcium homeostasis via ITGB3 receptor in murine sepsis-related cardiomyopathy","authors":"Yi-Ni Lu ,&nbsp;Wen-Xue Liu ,&nbsp;Xiao-Han Wang ,&nbsp;Xiong Zhang ,&nbsp;Yu-Fen Zheng ,&nbsp;Tian-Yin Wang ,&nbsp;Feng Chen ,&nbsp;Feng Yu","doi":"10.1016/j.bbamcr.2025.120083","DOIUrl":"10.1016/j.bbamcr.2025.120083","url":null,"abstract":"<div><div>Sepsis-related cardiomyopathy (SCM) is a life-threatening complication of sepsis, characterized by cardiac dysfunction. Although angiopoietin 2 (ANGPT2) is pivotal in the pathological progress of several diseases, its functional involvement in the pathogenesis of SCM remains uncharacterized. In this study, we demonstrated that ANGPT2 is a key regulator of SCM progression, bridging the functional homeostasis between vascular endothelial cells (ECs) and cardiomyocytes. Bioinformatics analysis of a SCM-related gene set derived from public databases revealed that ANGPT2 is a critical regulatory node. Serum ANGPT2 levels correlated with elevated creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) <em>in vivo</em>. Abnormal cardiac function was observed in cecal ligation and puncture (CLP)-induced sepsis mouse model and adeno-associated virus 9-mediated endothelial cell-specific ANGPT2-overexpressing (AAV9-<em>Angpt2</em>) mice, primarily characterized by reduced left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). Additionally, integrin β1 (ITGB1) and integrin β3 (ITGB3) were upregulated, along with dysregulation of calcium signaling-associated proteins in cardiac tissue. Notably, AAV9-<em>Angpt2</em> mice exhibited exacerbated CLP-induced cardiac dysfunction. <em>In vitro</em> experiments showed that ANGPT2 significantly reduced the beating frequency of primary neonatal mouse cardiomyocytes (NMCMs), and disrupted intracellular calcium homeostasis in adult mouse cardiomyocytes (AMCMs). Mechanistically, ANGPT2 activates and binds to the extracellular domains of ITGB3, thereby triggering ryanodine receptor 2 (RYR2) phosphorylation and upregulating the reticulum calcium ATPase 2 (ATP2a2) and phospholamban (PLN) expression, while simultaneously suppressing PLN phosphorylation. ITGB3-specific siRNA significantly attenuated the effects of ANGPT2 on calcium signaling proteins and intracellular calcium homeostasis. Collectively, these results suggest that the ANGPT2-ITGB3 signaling axis plays an important role in the pathogenesis of SCM in mice and may support this pathway as a potential therapeutic target during sepsis in humans.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1873 1","pages":"Article 120083"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450726","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}