Archives of biochemistry and biophysics最新文献

{"title":"Differential structural characteristics, physicochemical properties, and calcium-binding capabilities of annexin A2 wild-type versus E53A, E96A, D162A, E247A and D322A mutants.","authors":"Sunisa Yoodee, Sirikanya Plumworasawat, Thanyalak Malaitad, Paleerath Peerapen, Visith Thongboonkerd","doi":"10.1016/j.abb.2024.110267","DOIUrl":"10.1016/j.abb.2024.110267","url":null,"abstract":"<p><p>Annexin A2 (ANXA2) is a Ca²⁺-dependent multifunctional protein containing five Ca²⁺-binding domains, but their functional significance and difference remain unclear. Herein, glutamic acid (E) or aspartic acid (D) in five Ca²⁺-binding domains of canine ANXA2 (98.82 % and 96.76-99.41 % identical to ANXA2 from human and other mammals, respectively) was substituted by alanine (A) using site-directed mutagenesis. Recombinant ANXA2 wild-type (WT) and E53A, E96A, D162A, E247A and D322A mutants were constructed and expressed using a bacterial expression system followed by high-affinity purification using nickel-nitrilotriacetic acid (Ni-NTA) matrix. Efficacies of their expression and purification were confirmed by SDS-PAGE and Western blotting. Their amino acid sequences were verified by nanoLC-ESI-Qq-TOF tandem mass spectrometry. ATR-FTIR spectroscopy revealed that their secondary structure significantly differed (α-helix decreased but random coil increased in all mutants). Analyses of physicochemical properties revealed that molecular weight slightly decreased, whereas isoelectric point, aliphatic index, grand average of hydropathicity, electrostatic potential and molecular hydrophobicity potential slightly increased in all the mutants compared with WT. Interestingly, Ca²⁺-binding capability of these mutants (particularly E96A and D322A) significantly decreased from that of WT. In summary, secondary structure, physicochemical properties, and Ca²⁺-binding capability of E53A, E96A, D162A, E247A and D322A mutants of ANXA2 significantly differed from its WT, consistent with the loss of negatively charged E/D. In particular, E96A and D322A exhibited the lowest Ca²⁺-binding capability. These data and recombinant proteins would be useful for further investigations of the Ca²⁺-dependent functions of individual Ca²⁺-binding domains in ANXA2.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110267"},"PeriodicalIF":3.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823942","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":"Identification of ABC transporter Cdr1 inhibitors of Candida glabrata.","authors":"Mohd Waseem, Shubhashis Das, Debarati Mondal, Anuj Kumari, Ritu Kulshreshtha, Jitendra K Thakur, Naidu Subbarao","doi":"10.1016/j.abb.2024.110270","DOIUrl":"10.1016/j.abb.2024.110270","url":null,"abstract":"<p><p>Candida glabrata is one of the most common causes of invasive candidiasis. Rising treatment failures from resistance to current antifungal drugs highlight the need for new antifungals. Overexpression of efflux pump transporter genes is significantly associated with the development of multidrug resistance. In this study, we have identified novel and potential inhibitors of ABC transporter Cdr1 of Candida glabrata (CgCdr1) by employing high throughput virtual screening of large chemical datasets from five different chemical libraries (ZINC, DrugBank, ChemDiv antifungal, ChemDiv Kinases, and ChEMBL bioassay). As a result many molecules were predicted to have higher binding affinity toward the CgCdr1, in which a naturally occurring compound, pentagalloyl glucose, was identified to significantly reduce the growth of Candida glabrata with an IC₅₀ value of 16.97 ± 2.1 μM. Molecular dynamics studies showed stable binding of pentagalloyl glucose with CgCdr1 protein. In summary, our research identifies pentagalloyl glucose as a novel antifungal compound that has the potential to be used for inhibiting the growth of Candida glabrata.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110270"},"PeriodicalIF":3.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833759","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":"Oxidation of CaMKIIα cysteines inhibits autonomous activation induced by phosphorylation.","authors":"Nathália Rocco-Machado, Max Deng, Yi He, Rodney L Levine","doi":"10.1016/j.abb.2024.110268","DOIUrl":"10.1016/j.abb.2024.110268","url":null,"abstract":"<p><p>Ca²⁺/calmodulin-dependent protein kinase II α (CaMKIIα) \"autonomous\" activation induced by Thr286 phosphorylation has a crucial role in synaptic plasticity. Previous studies showed that in Alzheimer's disease brain, CaMKIIα autophosphorylation at Thr286 is reduced while the level of cysteine-oxidized CAMKIIα is elevated. We performed tryptic mapping of the oxidized CaMKIIα and discovered the formation of a disulfide between the N-terminal Cys6 and the regulatory domain Cys280. The apparent pK_a values of Cys6 and Cys280 are 7.1 and 7.7, respectively, lower than the 8.5 for free Cys. The low apparent pK_a of Cys6 facilitates the oxidation of its thiol to the sulfenic acid at physiological pH. The thiolate of Cys280 can then attack the sulfenic acid to form a disulfide. Using an antibody against phosphorylated Thr286, we showed that disulfide formation prevents Thr286 phosphorylation. CaMKIIα autonomous activation induced by disulfide formation is much lower than the autonomous activation induced by phosphorylation. The decreased autonomous activation may contribute to the synaptic impairment of Alzheimer's disease. We also generated a CaMKIIα mutant in which Cys6 was mutated to Ser6. This mutation prevented disulfide formation and restored autonomous activation induced by phosphorylation. Our findings provide insight into the mechanistic details of CaMKIIα autonomous activation induced by disulfide formation that may contribute to the impairment of long-term potentiation in Alzheimer's disease.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110268"},"PeriodicalIF":3.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823945","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":"Blueberry-derived exosome like nanovesicles carry RNA cargo into HIEC-6 cells and down-regulate LPS-induced inflammatory gene expression: a proof-of-concept study.","authors":"Sharon Natasha Cox, Vito Porcelli, Simona Romano, Luigi Palmieri, Deborah Fratantonio","doi":"10.1016/j.abb.2024.110266","DOIUrl":"https://doi.org/10.1016/j.abb.2024.110266","url":null,"abstract":"<p><p>Exosome-like nanovesicles (ELNs) of food origin have received great attention in the last decade, due to the hypothesis that they contain bioactive molecules. ELNs purified from edible species have been shown to be protective and are able to regulate intestinal homeostasis. Despite ELNs being potential rising stars in modern healthy diets and biomedical applications, further research is needed to address underlying knowledge gaps, especially related to the specific molecular mechanism through which they exert their action. Here, we investigate the cellular uptake of blueberry-derived ELNs (B-ELNs) using a human stabilized intestinal cell line (HIEC-6) and assess the ability of B-ELNs to modulate the expression of inflammatory genes in response to lipopolysaccharide (LPS). Our findings show that B-ELNs are internalized by HIEC-6 cells and transport labeled RNA cargo into them. Pretreatment with B-ELNs reduces LPS-induced ROS generation and cell viability loss, while modulating the expression of 28 inflammatory genes compared to control. Pathway analysis demonstrates their ability to suppress inflammatory responses triggered by LPS. In conclusion, our data indicate that B-ELNs are up taken by HIEC-6 cells and can modulate inflammatory responses after LPS stimulation, suggesting a therapeutic potential. This study demonstrates the role of B-ELNs in regulating crucial biological processes, like anti-inflammatory responses, which could support intestinal health.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110266"},"PeriodicalIF":3.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823930","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":"Radiosensitization impact assessment of silica-layered iron oxide nanocomposites with various shell thickness.","authors":"Mohamed M Fathy, Omnia A Saad, Heba M Fahmy","doi":"10.1016/j.abb.2024.110257","DOIUrl":"10.1016/j.abb.2024.110257","url":null,"abstract":"<p><p>Silica shell is considered to be a promising design that enhances nanocomposite stability, cellular internalization, and consequentially therapeutic impacts by overcoming their aggregation under physiological conditions. This study addressed synthesizing silica-layered iron oxide-based nanoparticles (SCINPs) with different shell thicknesses (1-SCINPs, 2-SCINPs, 3-SCINPs, and 4-SCINPs). Also, the impact of shell thickness on the nanoparticle's cellular internalization and the radio-sensitizing effect of prepared nano-formulations were assessed. The physical properties of the synthesized nanoparticles were examined using transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), vibrating sample magnetometry (VSM), and X-ray diffraction (XRD). Cytotoxicity assay, oxidative stress parameters, and comet assay were used to investigate the radio-sensitizing effect of various nanoformulations. Results revealed that the mean diameter of prepared oxide-based nanoparticles (INPs) was about 12.63 ± 1.36 nm, and the shell thickness for 1-SCINPs, 2-SCINPs, 3-SCINPs, and 4-SCINPs was 22.58 ± 3.51, 26.13 ± 1.40, 46.95 ± 3.10 and 60.30 ± 4.30 nm, respectively. Interestingly, we found that in cells treated with 40 μg/ml of INPs, their viability decreased to 44.6 %. Meanwhile, the viability was 41.69 % and 39.4 % for cells treated with 1-SCINPs and 2-SCINPs, respectively. This means that a thicker silica shell led to a decreased impact on radiosensitization. This was attributed to the influence of surface properties and size of SCINPs on their cellular uptake and the secondary electrons' entrapment within thicker shells upon radiation exposure. Cell viability test, comet assay and oxidative stress parameters show that 2-SCINPs formulations had the most potent radiosensitizing effect (with the highest dose enhancement factor equal to 2.1) when combined with radio-treatment. The results suggest that optimizing the silica shell thickness is critical for maximizing the therapeutic efficacy of SCINPs, with 2-SCINPs showing the highest radiosensitization effect.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110257"},"PeriodicalIF":3.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823974","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":"Retraction notice to \"Inhibition of carnitine palmitoyl transferase 1A-induced fatty acid oxidation suppresses cell progression in gastric cancer\" [Archiv. Biochem. Biophys. 696 (2020) 108664].","authors":"Liqiang Wang, Changfeng Li, Yumei Song, ZhenKun Yan","doi":"10.1016/j.abb.2024.110264","DOIUrl":"10.1016/j.abb.2024.110264","url":null,"abstract":"","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110264"},"PeriodicalIF":3.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811703","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":"Therapeutic potential of SMAD7 targeting miRNA in the pathogenesis of diabetic nephropathy.","authors":"V Pooja Rathan, K Bhuvaneshwari, G Nideesh Adit, S Kavyashree, N Thulasi, A V S Geetha, K L Milan, K M Ramkumar","doi":"10.1016/j.abb.2024.110265","DOIUrl":"10.1016/j.abb.2024.110265","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a common complication of diabetes and a leading cause of end-stage renal disease, characterized by progressive kidney fibrosis and inflammation. The transforming growth factor-beta (TGF-β) signaling pathway plays a crucial role in the pathogenesis of diabetes nephropathy, and SMAD7 is a key negative regulator of this pathway. Recent studies have highlighted the involvement of miRNA in the progression of DN. Computational analysis identified 11 potential miRNAs such as miR-424, miR-195, miR-216a, miR-503, miR-15a-5p, miR-15b-5p, miR-665, miR-520h, miR16-5p, miR-21 and miR-32-5p which are predicted to target 3'UTR of SMAD7 mRNA. This review aims to explore the role of these miRNAs in the progression of DN. Notably, these miRNAs have shown therapeutic potential in mitigating fibrosis and inflammation by modulating SMAD7 expression in DN. Future directions can be to investigate the mechanistic pathways through which these miRNAs exert their effects, as well as optimizing delivery systems for effective clinical application. Targeting miRNAs that modulate SMAD7 expression represents a promising strategy for developing specific and effective therapies for diabetic nephropathy.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110265"},"PeriodicalIF":3.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817070","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":"Corrigendum to \"LncRNA ZNF649-AS1 promotes trastuzumab resistance and TAM-dependent PD-L1 expression in breast cancer by regulating EXOC7 alternative splicing\" [Archiv. Biochem. Biophys. 761 (2024) 110128].","authors":"Huaying Dong, Jing Han, Xiang Chen, Hening Sun, Mingli Han, Wei Wang","doi":"10.1016/j.abb.2024.110220","DOIUrl":"https://doi.org/10.1016/j.abb.2024.110220","url":null,"abstract":"","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110220"},"PeriodicalIF":3.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805695","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":"FFA intervention on LO2 cells mediates SNX-10 synthesis and regulates MMP9 secretion in LX2 cells via TGF-β1.","authors":"Jianhui Xie, Shiyan Chen, Yangli Chen, Junlu Tong, Huijie Huang, Jingwen Liao, Jixin Sun, Li Cong, Yingjuan Zeng","doi":"10.1016/j.abb.2024.110255","DOIUrl":"10.1016/j.abb.2024.110255","url":null,"abstract":"<p><strong>Background: </strong>Metabolic-associated fatty liver disease (MAFLD) is a public health concern. Transforming growth factor-β1(TGF-β1) plays an important regulatory role in multiple MAFLD stages, as it can promote the expression of matrix metalloproteinase-9 (MMP9) and promote liver fibrosis. Sorting nexin protein-10 (SNX-10) may be involved in the occurrence and development of fatty liver disease.</p><p><strong>Methods: </strong>Free fatty acids (FFA) treatment was used to simulate the cellular lipid deposition stage of MAFLD and the interactions between cells were simulated via LX2 and LO2 coculture. The molecular interaction between the two cell types was studied via ELISA, immunoprecipitation, qPCR, and western blotting.</p><p><strong>Results: </strong>In FFA-treated LO2 cells, intracellular TGF-β1 expression increased as lipid deposition increased. FFA-treated LO2 cells promoted the expression and secretion of MMP9 by LX2 cells through paracrine pathways. MMP9 secretion decreased with decreasing SNX-10 expression in LX2 cells. The interaction between MMP9 and SNX-10 was confirmed by coimmunoprecipitation. TGF-β1 promoted the synthesis of SNX-10 through the p38 MAPK pathway, and SNX-10 affected the secretion of MMP9 through protein interactions, thereby affecting the development of liver fibrosis.</p><p><strong>Conclusions: </strong>FFA induced lipid deposition in LO2 cells, and TGF-β1 mediated the p38 MAPK pathway to promote SNX-10 synthesis and stimulate MMP9 secretion, thereby regulating the involvement of LX2 in the process of liver fibrosis.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110255"},"PeriodicalIF":3.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812036","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":"MD simulations for rational design of high-affinity HDAC4 inhibitors - Analysis of non-bonding interaction energies for building new compounds.","authors":"Varun Dewaker, Pratik Narain Srivastava, Utsab Debnath, Ajay Kumar Srivastava, Yenamandra S Prabhakar","doi":"10.1016/j.abb.2024.110262","DOIUrl":"10.1016/j.abb.2024.110262","url":null,"abstract":"<p><p>This study investigates the contributions of non-bonding energy (NBE) to the efficacy of four HDAC4 co-crystallized inhibitors (HA3, 9F4, EBE, and TFG) through 100ns Molecular Dynamics (MD) simulations. These inhibitors contain hydroxamic acid (HA3, 9F4, EBE) or diol (TFG) as zinc-binding groups. In PDBs 2VQJ and 2VQM, the HDAC4 catalytic domain is in the 'open' conformation, while in PDBs 4CBT and 6FYZ, the same is in the 'closed' conformation. We identified HA3 as a weaker inhibitor because of the unfavorable NBE contributions from its carbonyl fragment (FR3) and hydroxamic fragment (FR1). To enhance NBE efficacy, we designed novel HA3 analogs (H01-H16) by introducing diverse fragments (-CF3, 2-hydroxyacetic acid, -NH-CH2-, 5-fluoro-2-phenyl pyrimidine, and chloroquinoline moieties). MD simulations revealed promising analogs (H02, H07, H08, H15) with strong NBEs and stable ligand-zinc retention (2.07-2.33 Å). These analogs exhibited strong relative binding free energies within their catalytic sites, highlighting their potential as novel HDAC4 inhibitors. The current study provides medicinal chemists with insights into non-covalent interactions, identifies key fragments for optimization, and offers a rational design strategy for developing more effective HDAC4 inhibitors.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110262"},"PeriodicalIF":3.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811786","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}