Archives of biochemistry and biophysics最新文献

Exercise alleviates programmed necrosis in myocardial ischemia-reperfusion injury through adipose tissue-derived exosomal miR-17-3p targeting CAMKII 运动通过脂肪组织源性外泌体靶向CAMKII的miR-17-3p减轻心肌缺血再灌注损伤中的程序性坏死

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-10 DOI: 10.1016/j.abb.2025.110640

Zhuyuan Liu, Wenbin Lu, Yanru He, Fuchao Yu

{"title":"Exercise alleviates programmed necrosis in myocardial ischemia-reperfusion injury through adipose tissue-derived exosomal miR-17-3p targeting CAMKII","authors":"Zhuyuan Liu, Wenbin Lu, Yanru He, Fuchao Yu","doi":"10.1016/j.abb.2025.110640","DOIUrl":"10.1016/j.abb.2025.110640","url":null,"abstract":"<div><div>Exercise exerts cardioprotective effects, with prior research implicating exosomal miR-17-3p as a critical mediator in attenuating myocardial ischemia-reperfusion injury (MIRI). The present study aimed to elucidate the influence of exercise on exosomal miR-17-3p and to delineate the underly mechanisms by which it mitigates MIRI. A MIRI model was established using C57BL/6 mice. Exosomes were isolated and their impact on programmed necrosis, cardiac function, infarct size, inflammatory factors (LDH, TNF-α), as well as proteins associated with ventricular remodeling, was evaluated. Complementary in vitro experiments employed primary cardiomyocytes to further investigate these effects. The regulatory relationship between miR-17-3p and calcium/calmodulin-dependent protein kinase II (CAMK II) was examined. Additionally, the contribution of brown adipose tissue (BAT) as the source of exosomal miR-17-3p was assessed. Findings demonstrated that exercise enhanced cardiac function and reduced infarct size in MIRI mice through exosome-mediated mechanisms. Mechanistically, exosomal miR-17-3p directly targeted CAMKII, leading to inhibition of the RIPK3/MLKL pathway, thereby attenuating cardiomyocyte necrosis and inflammation and reversing pathological ventricular remodeling. BAT was identified as the principal origin of exosomal miR-17-3p, and ablation of BAT abrogated the cardioprotective effects conferred by exercise. Collectively, these results suggest that exercise confers protection against MIRI by promoting the uptake of BAT-derived exosomal miR-17-3p uptake by cardiomyocytes, which in turn supresses CAMKII activity and programmed necrosis. This study reveals a novel exercise-induced cardioprotective pathway and identifies potential therapeutic targets for MIRI.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110640"},"PeriodicalIF":3.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262977","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}

引用次数: 0

Mechanism of vascular endothelial growth factor regulating hypoxia and inflammatory microenvironment in endometriosis: based on bioinformatics and multi-level validation. 血管内皮生长因子调节子宫内膜异位症缺氧和炎症微环境的机制：基于生物信息学和多层次验证。

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-10 DOI: 10.1016/j.abb.2025.110639

Weichang Yu

{"title":"Mechanism of vascular endothelial growth factor regulating hypoxia and inflammatory microenvironment in endometriosis: based on bioinformatics and multi-level validation.","authors":"Weichang Yu","doi":"10.1016/j.abb.2025.110639","DOIUrl":"https://doi.org/10.1016/j.abb.2025.110639","url":null,"abstract":"Endometriosis remains a prevalent gynecological disorder that affects women during their reproductive years, featured by progressive inflammation and enhanced HIF-1α expression. This paper intended to plumb the mechanism of vascular endothelial growth factor (VEGF) in endometriosis. To this end, the differential expression of VEGF as well as the correlation between VEGF and inflammation-related genes was initially analyzed via bioinformatics approaches. GO and KEGG pathway analyses were implemented to determine the main signaling pathways. RT-qPCR, western blot and ELISA were implemented to assess VEGF, HIF-1α and IL-33 levels. Transwell, together with CCK-8 assay examined the capabilities of 12Z cells to invade and proliferate. To establish the rat model of endometriosis, autologous endosomal transplantation approach was used. Through liquid suspension chip technology, the levels of pro-inflammatory cytokines were appraised. Immunofluorescence assay examined the production of VEGF, HIF-1α and CD68 in ectopic endometrial tissues. The bioinformatics analysis unmasked that VEGF expression was elevated in endometriosis tissues and VEGF had positive correlation with HIF1A and IL-33. GO enrichment analysis demonstrated that VEGF was implicated in hypoxia and inflammation-related processes. The in vitro experiments illustrated that VEGF silence could reduce HIF-1α, IL-33, TNF-α and IL-6 expression, and suppress 12Z cell proliferation and invasion. Analysis of clinical samples manifested that VEGF level in serum was enhanced. Moreover, the in vivo experiments presented that Bevacizumab could improve the inflammatory state and lesion growth. Collectively, this paper validated the critical role of VEGF in regulating hypoxia and inflammatory microenvironment in endometriosis and identified novel prospective targets for endometriosis alleviation.","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110639"},"PeriodicalIF":3.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278745","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}

引用次数: 0

Thermodynamics of the transition from the ferryl (F) state to the oxidized form of the solubilized cytochrome c oxidase: implication for the proton pumping. 可溶性细胞色素c氧化酶从铁基(F)态到氧化态转变的热力学：对质子泵送的启示。

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-08 DOI: 10.1016/j.abb.2025.110638

Adriana Tomkova, Tereza Sztachova, Jonatan Johannesson, Daniel Jancura, Marian Fabian

{"title":"Thermodynamics of the transition from the ferryl (F) state to the oxidized form of the solubilized cytochrome c oxidase: implication for the proton pumping.","authors":"Adriana Tomkova, Tereza Sztachova, Jonatan Johannesson, Daniel Jancura, Marian Fabian","doi":"10.1016/j.abb.2025.110638","DOIUrl":"https://doi.org/10.1016/j.abb.2025.110638","url":null,"abstract":"Two ferryl intermediates have been identified in the membrane-bound respiratory heme-copper oxygen reductases (HCOs) during reduction of O2 to water. Apparently, energy released by reduction of these two ferryl forms is utilized to build the transmembrane electrochemical proton gradient by two mechanisms. One of them, the proton pumping, is the key unresolved problem of the contemporary molecular bioenergetics. Even though the position of these ferryl forms in energy transformation is central, the direct and complete thermodynamic characterization of these intermediates is lacking. Here, thermodynamics of redox transition of one of these ferryl intermediates, the F state, was established by isothermal titration calorimetry (ITC) and density functional theory utilizing one representative of HCOs, bovine cytochrome c oxidase (CcO). In CcOs, the reduction of catalytic cytochrome a3-CuB center is accomplished by electron transfer (ET) from ferrocytochrome c via copper CuA and cytochrome a center. The energy for the pumping is suggested to be released mainly during the transition of the catalytic center of F initiated by ET from cytochrome a. This transfer results in the conversion of Fe(IV)=O to Fe(III) state of heme a3, yielding the oxidized CcO (O). Based on the enthalpy changes determined by ITC and available entropy values for this process, the estimated ΔG0 was found to be -24 kcal/mol, corresponding to the electrode potential of +1.3 V for the F/O couple (pH 8.0, 25 °C). Remarkably, the results indicate that major fraction of energy for the proton pumping is provided by the redox-dependent structural changes of cytochrome a.","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110638"},"PeriodicalIF":3.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273518","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}

引用次数: 0

A novel tRNA-Derived Fragment, tRF-23-Z87HFK8SDZ inhibits malignant progression of pancreatic cancer through mediating IRS1. 一个新的trna衍生片段，tRF-23-Z87HFK8SDZ通过介导IRS1抑制胰腺癌的恶性进展。

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-08 DOI: 10.1016/j.abb.2025.110624

Liping Zheng, Jing Wang, Yiyu Shen, Chundong Hu, Bin Wu, Zhongcheng Zhou, Wei Wang

{"title":"A novel tRNA-Derived Fragment, tRF-23-Z87HFK8SDZ inhibits malignant progression of pancreatic cancer through mediating IRS1.","authors":"Liping Zheng, Jing Wang, Yiyu Shen, Chundong Hu, Bin Wu, Zhongcheng Zhou, Wei Wang","doi":"10.1016/j.abb.2025.110624","DOIUrl":"https://doi.org/10.1016/j.abb.2025.110624","url":null,"abstract":"Background: Transfer RNA-derived fragments (tRFs) have emerged as significant actors in cancer progression. Nevertheless, their functions in pancreatic cancer stay poorly understood. This work focuses on the role of tRF-23-Z87HFK8SDZ (tRF-23), a downregulated fragment in pancreatic cancer, and its potential tumor-suppressive functions through the regulation of IRS1.Methods: RNA sequencing was performed on cancerous and adjacent non-cancerous tissues from pancreatic cancer patients to identify differentially expressed tRFs. RT-qPCR, Kaplan-Meier survival analysis, and various in vivo and in vitro functional assays were performed to assess tRF-23 expression, its effects on cellular processes, and its regulation of IRS1. Dual-luciferase and RNA immunoprecipitation assays proved the interaction between tRF-23 and IRS1.Results: tRF-23 was considerably downregulated in pancreatic cancer tissues and cells. Lower tRF-23 expression was correlated with poor patient survival. Overexpression of tRF-23 inhibited cell viability, proliferation, and migration, while advancing cell cycle arrest and apoptosis in pancreatic cancer cells. In vivo, tRF-23 reduced tumor growth in a subcutaneous mouse model. tRF-23 directly targeted IRS1, downregulating its protein and mRNA levels, and IRS1 overexpression partially rescued these effects.Conclusion: tRF-23 suppresses the malignant progression of pancreatic cancer by downregulating IRS1. These findings suggest that the tRF-23/IRS1 axis could act as a prospective therapeutic target in pancreatic cancer.","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110624"},"PeriodicalIF":3.0,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273559","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}

引用次数: 0

Novel epigenetic biomarkers following ferroptosis and pyroptosis in a hypobaric hypoxia-induced renal injury model. 在低压缺氧诱导的肾损伤模型中，铁下垂和焦下垂后的新表观遗传生物标志物。

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-07 DOI: 10.1016/j.abb.2025.110637

Hongxuan Liu, Huishu Lin, Yuhong He, Shuhao Shi, Jiayan Ni, Lei Zhao, Yuxuan Ma, Weixia Li, Yuanyuan Yu, Chen Li, Qisijing Liu, Shike Hou, Xiaoxue Li, Liqiong Guo

{"title":"Novel epigenetic biomarkers following ferroptosis and pyroptosis in a hypobaric hypoxia-induced renal injury model.","authors":"Hongxuan Liu, Huishu Lin, Yuhong He, Shuhao Shi, Jiayan Ni, Lei Zhao, Yuxuan Ma, Weixia Li, Yuanyuan Yu, Chen Li, Qisijing Liu, Shike Hou, Xiaoxue Li, Liqiong Guo","doi":"10.1016/j.abb.2025.110637","DOIUrl":"https://doi.org/10.1016/j.abb.2025.110637","url":null,"abstract":"Background: Rapid hypobaric hypoxia exposure damages oxygen-sensitive organs like the kidneys. Ferroptosis and pyroptosis, oxygen-dependent cell death mechanisms, remain understudied in this context, as does the role of mitochondrial DNA (mtDNA) methylation.Methods: We established a rat model of hypobaric hypoxia (6000m/7000m, 6h/72h). Kidney ferroptosis (Prussian blue staining, LPO/MDA/GSH assays, ACSL4/GPX4 expression) and pyroptosis (Caspase1/GSDMD activation) were analyzed. mt-cox1/2/3 methylation was assessed in renal mitochondrial DNA, cytoplasmic DNA, and serum cell-free DNA (cf mtDNA) via pyrosequencing. PCA identified biomarkers.Results: Hypobaric hypoxia induced renal iron accumulation, lipid peroxidation, and tubular injury. Ferroptosis was mediated by ACSL4 upregulation and GPX4 suppression, while pyroptosis activated Caspase1/GSDMD. Mitochondrial damage and mtDNA leakage were observed via TEM. mt-cox3 pos2 hypermethylation in serum cell-free mtDNA distinctly distinguished hypoxia-exposed rats via PCA.Conclusion: Ferroptosis and pyroptosis synergize to drive hypobaric hypoxia-induced renal injury. mt-cox3 pos2 methylation in cell-free mtDNA emerges as a novel biomarker for renal pathogenesis.","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110637"},"PeriodicalIF":3.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257206","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}

引用次数: 0

MITOCHONDRIAL REDOX IMBALANCE AND CoQ₁₀ DEFICIENCY IN RETT SYNDROME: INSIGHTS FROM PATIENT-DERIVED FIBROBLASTS. RETT综合征的线粒体氧化还原失衡和辅酶q10缺乏：来自患者来源的成纤维细胞的见解。

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-06 DOI: 10.1016/j.abb.2025.110636

Francesco Mengarelli, Valeria Cordone, Alessandra Pecorelli, Mascia Benedusi, Giuseppe Valacchi, Camilla Morresi, Tiziana Bacchetti, Patrick Orlando, Luca Tiano, Sonia Silvestri

{"title":"MITOCHONDRIAL REDOX IMBALANCE AND CoQ10 DEFICIENCY IN RETT SYNDROME: INSIGHTS FROM PATIENT-DERIVED FIBROBLASTS.","authors":"Francesco Mengarelli, Valeria Cordone, Alessandra Pecorelli, Mascia Benedusi, Giuseppe Valacchi, Camilla Morresi, Tiziana Bacchetti, Patrick Orlando, Luca Tiano, Sonia Silvestri","doi":"10.1016/j.abb.2025.110636","DOIUrl":"https://doi.org/10.1016/j.abb.2025.110636","url":null,"abstract":"Rett syndrome (RTT), a neurodevelopmental disorder primarily affecting females, is characterized by mutations in the MECP2 gene, leading to systemic oxidative stress and mitochondrial dysfunction. This study investigates the role of Coenzyme Q10 (CoQ10), particularly its reduced form ubiquinol, in modulating oxidative stress and mitochondrial function in primary dermal fibroblasts derived from RTT patients with distinct MeCP2 mutations. Baseline assessments revealed significant CoQ10 deficiencies and elevated reactive oxygen species (ROS) levels, notably in fibroblasts with the T158M mutation. Ubiquinol supplementation effectively restored CoQ10 levels and improved redox balance in these cells. Additionally, treatment influenced mitochondrial dynamics, as evidenced by alterations in the expression of fission and fusion proteins and modulated the activity of paraoxonase 2 (PON2), an enzyme involved in cellular antioxidant defense. In conclusion, our data suggest that CoQ10 supplementation could mitigate oxidative damage and preserve mitochondrial integrity, but we are far from being able to claim that it can represents an effective therapeutic strategy to complement current pharmacological treatments in RTT patients. Further research is warranted to explore the potential of CoQ10 as an adjunctive treatment, particularly during the early stages of RTT.","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110636"},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249352","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}

引用次数: 0

Lauryl gallate induces apoptosis via p38-MAPK phosphorylation and autophagy in chemoresistant human lung cancer cells 没食子酸月桂酯通过p38-MAPK磷酸化和自噬诱导化疗耐药人肺癌细胞凋亡。

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-06 DOI: 10.1016/j.abb.2025.110633

Yen-Hsiang Huang , Shur-Hueih Cherng , Ling-Yen Chiu , Kuo-Hsuan Hsu , Jeng-Sen Tseng , Po-Hsin Lee , Gwo-Tarng Sheu , Tsung-Ying Yang

{"title":"Lauryl gallate induces apoptosis via p38-MAPK phosphorylation and autophagy in chemoresistant human lung cancer cells","authors":"Yen-Hsiang Huang , Shur-Hueih Cherng , Ling-Yen Chiu , Kuo-Hsuan Hsu , Jeng-Sen Tseng , Po-Hsin Lee , Gwo-Tarng Sheu , Tsung-Ying Yang","doi":"10.1016/j.abb.2025.110633","DOIUrl":"10.1016/j.abb.2025.110633","url":null,"abstract":"<div><div>Human lung cancer has taken many lives and chemoresistance generally occurs in patients and reduces patients’ survival. Docetaxel (DOC) and vincristine (VCR) have been widely used in cancer chemotherapy but their efficacy is restricted by P-glycoprotein (P-gp) overexpression. Lauryl gallate (LG) is a plant-derived small molecule which acts as antioxidant in normal cells. Surprisingly, LG also has been shown to control several types of cancer cells and induce apoptosis by way of induction of reactive oxygen species (ROS). To further clarify the anti-lung cancer activity of LG, we evaluated the cytotoxicity of LG using a previously established human A549/DOC resistant subline that has high P-gp expression and a A549/VCR resistant subline to determine their LG sensitivity by MTT assay. The apoptosis and autophagy levels were examined by protein analysis and flow cytometry. Interference of p38-MAPK and ATG5 expression by siRNAs was performed to measure the involvement of these two proteins in apoptosis and autophagy. We found that LG exerts higher cytotoxicity to the target cells when compared with tannic acid (TA) and octyl gallate (OG). Furthermore, LG not only induces apoptosis, it also enhances autophagy in both chemoresistant A549 sublines. When p38-MAPK was knocked down, the apoptosis level was reduced but autophagy was not. Knockdown of ATG5 resulted in significant apoptosis reduction in VCR-resistant A549 cells but less effect was found in DOC-resistant A549 cells. In sum, our data suggested that LG promotes p38-MAPK phosphorylation and induces apoptosis in chemoresistant A549 cells independently with P-gp expression. LG also enhances autophagy-regulated cell death in chemoresistant lung cancer cells.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110633"},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249370","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}

引用次数: 0

Study of the antibacterial peptide P8.1: Effect on anionic vesicles using spectroscopic techniques. 利用光谱技术研究抗菌肽P8.1对阴离子囊泡的影响。

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-04 DOI: 10.1016/j.abb.2025.110635

Luis Emanuel Jimenez, Rosa M S Álvarez, Paulo Maffia, Axel Hollmann

{"title":"Study of the antibacterial peptide P8.1: Effect on anionic vesicles using spectroscopic techniques.","authors":"Luis Emanuel Jimenez, Rosa M S Álvarez, Paulo Maffia, Axel Hollmann","doi":"10.1016/j.abb.2025.110635","DOIUrl":"https://doi.org/10.1016/j.abb.2025.110635","url":null,"abstract":"Antimicrobial peptides (AMPs) are promising complements to antibiotics, yet their membrane-level actions remain incompletely understood. In this work, we characterized how the \"de novo\" cationic AMP P8.1 interacts with anionic lipid bilayers composed of DPPG (gel phase) or DLPG (fluid phase) using zeta potential, tryptophan and Laurdan fluorescence, Raman microscopy, and a carboxyfluorescein (CF) leakage assay. P8.1 bound both lipids electrostatically, reduced zeta potential, and increased large unilamellar vesicles (LUVs) size. Binding kinetics were faster on DPPG multilamellar vesicles, whereas Trp fluorescence assays showed deeper insertion in DLPG (larger Trp blue-shift and lower acrylamide quenching). Laurdan generalized polarization (GP) increased in DLPG but not in DPPG, indicating reduced water access and higher local order in fluid bilayers. Raman spectra revealed diminished phosphate-band intensity in both systems and, in DLPG, a decreased gauche/trans ratio and narrower 1300 cm-1 band consistent with tighter acyl-chain packing. Difference spectra further showed an amide I shift of P8.1, supporting a random-coil to α-helix transition upon binding to lipids. Finally, P8.1 induced ∼80% CF leakage in DLPG LUVs within minutes. Together, the data indicate that P8.1 engages phosphate groups of lipids and then modulates bilayer structure in a phase- and mechanics-dependent manner-rigidifying short-chain, fluid DLPG and minimally perturbing gel-phase DPPG-providing mechanistic insight relevant to antibacterial activity.","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110635"},"PeriodicalIF":3.0,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237784","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}

引用次数: 0

Swapped domain orders in ZO-1 PDZ3 fusion proteins – implications for binding of established and novel targets ZO-1 PDZ3融合蛋白的交换结构域顺序-对已建立和新靶标结合的影响。

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-03 DOI: 10.1016/j.abb.2025.110634

Marie Hamsikova , Jan Hurdalek , Leandro Simonetti , Jakub Ptacek , Kristyna Vydra Bousova , Jiri Vondrasek , Ylva Ivarsson , Lucie Zemanova

{"title":"Swapped domain orders in ZO-1 PDZ3 fusion proteins – implications for binding of established and novel targets","authors":"Marie Hamsikova , Jan Hurdalek , Leandro Simonetti , Jakub Ptacek , Kristyna Vydra Bousova , Jiri Vondrasek , Ylva Ivarsson , Lucie Zemanova","doi":"10.1016/j.abb.2025.110634","DOIUrl":"10.1016/j.abb.2025.110634","url":null,"abstract":"<div><div>PDZ domains play key roles in mediating protein-protein interactions by recognizing short PDZ-binding motifs, typically at the C-termini of target proteins. Zonula occludens 1 (ZO-1) is a scaffolding protein that links tight junction proteins to the actin cytoskeleton, and contains three PDZ domains. Here, we focus on its third PDZ (PDZ3_ZO-1) domain, which interacts with the C-terminus of junctional adhesion protein A as well as connexin 45. To investigate how the domain context of the PDZ3_ZO-1 domain affects its folding and function, we previously established two distinct fusions of PDZ3_ZO-1 and a Trp-cage mini-protein. These fusions with swapped domain order result in FD3A with Trp-cage fused C-terminally and FD4A with Trp-cage fused N-terminally. This study aims to explore the extent to which the distinct Trp-cage fusions affect the function of PDZ3_ZO-1 domain in peptide binding.</div><div>We find that PDZ3_ZO-1 retains its function, interaction with the connexin 45 peptide, also as part of the fusion proteins. Furthermore, using a phage display approach, we identified a new PDZ3_ZO-1 binding peptide derived from the C-terminal region of methylcytosine dioxygenase TET3. Subsequent validation revealed a significantly higher affinity of PDZ3_ZO-1 for the TET3 peptide as compared to the connexin 45 peptide. Thermodynamic analyses revealed that the swapped domain order conferred distinct effects on the thermodynamic parameters. These results provide insights into the structural and functional adaptability of PDZ domains in engineered proteins, and offer useful principles for the rational design of functional fusion proteins.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110634"},"PeriodicalIF":3.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231391","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}

引用次数: 0

Multifunctional benzimidazolium derivatives as anticancer, antibacterial, and acetylcholinesterase inhibitors: In vitro and molecular docking studies 多功能苯并咪唑衍生物作为抗癌、抗菌和乙酰胆碱酯酶抑制剂：体外和分子对接研究。

IF 3 3区生物学

Archives of biochemistry and biophysics Pub Date : 2025-10-02 DOI: 10.1016/j.abb.2025.110630

Metin Yıldırım , Hakan Ünver , Adem Necip , Mehmet Çimentepe , Mehmet Ersatir

{"title":"Multifunctional benzimidazolium derivatives as anticancer, antibacterial, and acetylcholinesterase inhibitors: In vitro and molecular docking studies","authors":"Metin Yıldırım , Hakan Ünver , Adem Necip , Mehmet Çimentepe , Mehmet Ersatir","doi":"10.1016/j.abb.2025.110630","DOIUrl":"10.1016/j.abb.2025.110630","url":null,"abstract":"<div><div>In this study, a series of benzimidazolium derivatives were synthesized and characterized using HR-MS, FTIR, 1H NMR, and 13C NMR techniques. Their acetylcholinesterase (AChE) inhibitory potentials, anticancer activities against MCF-7 breast cancer cells, and antibacterial effects against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, as well as resistant strains such as MRSA and MDR Escherichia coli were experimentally evaluated. Additionally, their antibiofilm activities against MRSA and MDR E. coli were also assessed. These experimental findings were further supported by molecular docking studies. Among the tested compounds, compound 6c exhibited the highest AChE inhibitory activity, with an IC50 value of 9.32 μM. It also demonstrated the most potent anticancer activity against MCF-7 cells, with an IC50 value of 1.8 μM. All synthesized compounds exhibited antibacterial activity against both drug-resistant and non-resistant bacterial strains. Furthermore, compound 6c showed the strongest molecular docking interactions with AChE and MRSA-associated proteins, with binding energy scores of −9.386 kcal/mol (4EY7), −8.180 kcal/mol (1 ZGC), and −6.301 kcal/mol (3ZG5), respectively. This is the first report integrating AChE inhibition, anticancer, antibacterial, and antibiofilm evaluations of novel benzimidazolium derivatives in combination with molecular docking, thereby providing a multi-targeted framework for the development of new therapeutic agents against neurodegenerative diseases, cancer, and multidrug-resistant infections.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110630"},"PeriodicalIF":3.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228434","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}

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