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Identification and characterization of a laterally transferred alternative oxidase (AOX) in a terrestrial insect, the dipteran Pseudolycoriella hygida 陆生昆虫双翅目水合假科里菌(Pseudolycoriella hygida)体内横向转移替代氧化酶(AOX)的鉴定和表征。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-21 DOI: 10.1016/j.biochi.2025.02.007
Nadia Monesi , Guilherme Magre Fernandes , Felipe Berti Valer , João Vítor Cardoso Uliana , Vitor Trinca , Ana Elisa Caleiro Seixas Azzolini , Eduardo Gorab , Luciane Carla Alberici
{"title":"Identification and characterization of a laterally transferred alternative oxidase (AOX) in a terrestrial insect, the dipteran Pseudolycoriella hygida","authors":"Nadia Monesi ,&nbsp;Guilherme Magre Fernandes ,&nbsp;Felipe Berti Valer ,&nbsp;João Vítor Cardoso Uliana ,&nbsp;Vitor Trinca ,&nbsp;Ana Elisa Caleiro Seixas Azzolini ,&nbsp;Eduardo Gorab ,&nbsp;Luciane Carla Alberici","doi":"10.1016/j.biochi.2025.02.007","DOIUrl":"10.1016/j.biochi.2025.02.007","url":null,"abstract":"<div><div>Alternative oxidase (AOX) (EC 1.10.3.11) is a terminal oxidase in the mitochondrial inner membrane that branches the canonical electron transport system (ETS). AOX is ubiquitous in plants, frequently found in fungi and protists and presents a more sporadic distribution in metazoans. More recently, AOX has gained attention due to its potential application in gene therapy for treatment of mitochondrial diseases. Here we characterized the AOX in the basal Dipteran, <em>Pseudolycoriella hygida</em> using a combination of genomic analyses, molecular, functional and <em>in vivo</em> survival assays. <em>AOX</em> is a single copy gene that encodes three developmental stage specific protein isoforms. AOX localizes to the mitochondria in adult thoracic muscles, which present cyanide-resistant respiration that is sensitive to the AOX inhibitor salicylhydroxamic acid (SHAM). Both the cyanide-resistant respiration and AOX levels gradually increase during aging, but are not influenced by thermal stress. Thoracic mitochondria respire using substrates derived from several metabolic routes, such as pyruvate, proline, acylcarnitine, NADH and glycerol-3P, and present values of oxidative phosphorylation capacity ((P-L)/E = 0.70) and coupling (P/L = 4.35; L/E = 0.21). Adult flies exhibit a high survival resistance for SHAM-sensitive complex III inhibition. Together, our results demonstrate the presence of a functional AOX in a terrestrial arthropod and provide insights regarding AOX function in animals and evolution of respiratory systems in metazoans. <em>Psl. hygida</em> emerges as a natural and valuable model for comprehensive AOX research at the whole-organism level which complements models expressing the heterologous enzyme.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"233 ","pages":"Pages 60-74"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485011","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
Nitazoxanide inhibits pili assembly by targeting BamB to synergize with polymyxin B against drug-resistant Escherichia coli Nitazoxanide通过靶向BamB与多粘菌素B协同靶向耐药大肠杆菌抑制菌毛组装。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-19 DOI: 10.1016/j.biochi.2025.02.006
Wenwen Li , Bingjie Ji , Boyu Li, Minghui Du, Linwei Wang, Jiale Tuo, Hongmei Zhou, Jian Gong, Yongshan Zhao
{"title":"Nitazoxanide inhibits pili assembly by targeting BamB to synergize with polymyxin B against drug-resistant Escherichia coli","authors":"Wenwen Li ,&nbsp;Bingjie Ji ,&nbsp;Boyu Li,&nbsp;Minghui Du,&nbsp;Linwei Wang,&nbsp;Jiale Tuo,&nbsp;Hongmei Zhou,&nbsp;Jian Gong,&nbsp;Yongshan Zhao","doi":"10.1016/j.biochi.2025.02.006","DOIUrl":"10.1016/j.biochi.2025.02.006","url":null,"abstract":"<div><div>Gram-negative bacteria rely on pili assembly for pathogenicity, with the chaperone-usher (CU) pathway regulating pilus biogenesis. Nitazoxanide (NTZ) inhibits CU pathway-mediated P pilus biogenesis by specifically interfering with the proper folding of the outer membrane protein (OMP) usher, primarily mediated by the β-barrel assembly machinery (BAM) complex. In this study, we identified the BAM complex components BamB and the BamA POTRA2 domain as key binding targets for NTZ. Molecular dynamics simulations and Bio-Layer Interferometry revealed that BamB residues S61 and R195 are critical for NTZ binding. NTZ activated the Cpx two-component system and induced inner membrane perturbations, which resulted from the accumulation of misfolded P pilus subunits. Upregulation of the <em>ibpAB</em> gene, which protects the bacteria against NTZ-induced oxidative stress, was also observed. Importantly, NTZ combined with polymyxin B enhanced the latter's antibacterial activity against both susceptible and MCR-positive <em>E. coli</em> strains. This enhancement was achieved through NTZ-induced increases in inner membrane permeability, oxidative stress, and inhibition of efflux pump activity and biofilm formation. This study provides new insights into the antimicrobial mechanism of NTZ and highlights its potential as an antibiotic adjuvant by targeting BamB to inhibit the CU pathway, restoring the efficacy of polymyxin B against multidrug-resistant bacteria.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"233 ","pages":"Pages 47-59"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473204","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
Crystal structure of Leishmania orientalis triosephosphate isomerase at 1.88 Å resolution and its specific inhibitors 1.88 Å分辨率下东方利什曼原虫三磷酸异构酶的晶体结构及其特异性抑制剂。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-19 DOI: 10.1016/j.biochi.2025.02.004
Buabarn Kuaprasert , Ubolsree Leartsakulpanich , Pinpunya Riangrungroj , Wichai Pornthanakasem , Wipa Suginta , Mathirut Mungthin , Saovanee Leelayoova , Duangnapa Kiriwan , Kiattawee Choowongkomon
{"title":"Crystal structure of Leishmania orientalis triosephosphate isomerase at 1.88 Å resolution and its specific inhibitors","authors":"Buabarn Kuaprasert ,&nbsp;Ubolsree Leartsakulpanich ,&nbsp;Pinpunya Riangrungroj ,&nbsp;Wichai Pornthanakasem ,&nbsp;Wipa Suginta ,&nbsp;Mathirut Mungthin ,&nbsp;Saovanee Leelayoova ,&nbsp;Duangnapa Kiriwan ,&nbsp;Kiattawee Choowongkomon","doi":"10.1016/j.biochi.2025.02.004","DOIUrl":"10.1016/j.biochi.2025.02.004","url":null,"abstract":"<div><div><em>Leishmania orientalis</em>, previously called <em>L. siamensis</em>, is a new species characterized as causing cutaneous leishmaniasis in Thailand. This study solves the crystal structure of the <em>L. orientalis</em> triosephosphate isomerase (<em>Lo</em>TIM) in apo form at 1.88 Å resolution by using molecular replacement method. Tyrosine118 presents in the LoTIM protein sequence, whereas <em>L. mexicana</em> and <em>Trypanosoma cruzi</em> TIMs have a relative Cys118, which plays a major role in their specific ligand binding. Sulfur atom of the Cys57 thiol group is covalently bound to an arsenic (As) atom present in the precipitating solution. Although the electron density of loop-6 (Gly174-Tyr175-Gly176-Lys177-Val178) is missing in the structure due to this region lacking rigidity, the biological assembly of the two monomers of the <em>Lo</em>TIM crystal structures are like that of <em>L. mexicana</em> and <em>T. cruzi</em>. 3D molecular protein-ligand docking was performed using the dimeric interfacial pocket of the enzyme as a ligand-binding receptor to identify its specific inhibitors. Five potential inhibiting compounds, including NSC639174, NSC606498, NSC110039, NSC58446, and NSC345647, were obtained with their <em>IC</em><sub>50</sub> 2.79 ± 0.10, 3.28 ± 0.80, 3.67 ± 0.11, 4.59 ± 0.87 and 15.44 ± 0.14 μM, respectively. However, specific inhibition assays against TIMs from <em>L. orientalis</em> and rabbit muscle indicate that NSC639174 and NSC110039 are the most potent inhibitors for <em>Lo</em>TIM, whereas NSC58446 inhibits well both the parasitic and rabbit enzymes.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"233 ","pages":"Pages 27-35"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473266","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
The prolyl oligopeptidase and α-synuclein connection revisited 重新审视脯氨酸寡肽酶和α-突触核蛋白的联系。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-19 DOI: 10.1016/j.biochi.2025.02.003
Roos Van Elzen , Yannick Waumans , Sangeeta Nath , Pieter Van der Veken , Sonja Kerkhoff , Evert Van Dijk , Markus Morawski , Steffen Roßner , Yves Engelborghs , Ingrid De Meester , Anne-Marie Lambeir
{"title":"The prolyl oligopeptidase and α-synuclein connection revisited","authors":"Roos Van Elzen ,&nbsp;Yannick Waumans ,&nbsp;Sangeeta Nath ,&nbsp;Pieter Van der Veken ,&nbsp;Sonja Kerkhoff ,&nbsp;Evert Van Dijk ,&nbsp;Markus Morawski ,&nbsp;Steffen Roßner ,&nbsp;Yves Engelborghs ,&nbsp;Ingrid De Meester ,&nbsp;Anne-Marie Lambeir","doi":"10.1016/j.biochi.2025.02.003","DOIUrl":"10.1016/j.biochi.2025.02.003","url":null,"abstract":"<div><div>The aim of this work was to revisit the connection between prolyl oligopeptidase (PREP) and α-synuclein (aSyn) by presenting novel data from cell free and cellular assays and to discuss the results in a contemporary context.</div><div>The aSyn aggregation process was studied using fluorescence correlation spectroscopy and thioflavin-T fluorescence. Binding sites for PREP on the aSyn sequence were determined using peptide arrays. Subcellular localisation of PREP and stress markers were studied using double staining immunofluorescence microscopy in SH-SY5Y cells with and without overexpression of aSyn and PREP, before and after differentiation, and with or without proteolytic stress induced by proteasome inhibition.</div><div>The interaction between PREP and aSyn was found to be weak and transient. It promotes the early phases of aggregation but does not affect the rate of β-fibril formation. Moreover, this interaction is not dependent upon the C-terminal prolines of aSyn, but is affected by PREP inhibitors and interferes with PREP substrate binding. Although present in the same cellular compartments, there is little evidence for a strong physical association of PREP with aggresomes and stress markers. Instead, there is colocalization with aSyn in the cell periphery and neurites.</div><div>There is evidence for a binding site for peptides much longer than the usual PREP substrates. The modular assembly of molecular machines and the observation that PREP's protein-protein interactions are tuneable by active site inhibitors, lead to the hypothesis that this binding site features in the cross-talk between autophagy and neuron-specific pathways involving vesicle transport and protein secretion.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"233 ","pages":"Pages 1-13"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473206","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
Editor's Note to '27-hydroxycholesterol decreases cell proliferation in colon cancer cell lines' [Biochimie 153 (2018) 171-180] 编者按。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-06 DOI: 10.1016/j.biochi.2025.02.001
{"title":"Editor's Note to '27-hydroxycholesterol decreases cell proliferation in colon cancer cell lines' [Biochimie 153 (2018) 171-180]","authors":"","doi":"10.1016/j.biochi.2025.02.001","DOIUrl":"10.1016/j.biochi.2025.02.001","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"232 ","pages":"Page 142"},"PeriodicalIF":3.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374985","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
Fluor NMR study of amino acid derived ligand to study TSPO 氨基酸衍生配体的荧光核磁共振研究TSPO。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-04 DOI: 10.1016/j.biochi.2025.01.015
Luminita Duma , Severine Schneider , Agathe Martinez , Cathy Hachet , Frederic Bihel , Jean-Jacques Lacapere
{"title":"Fluor NMR study of amino acid derived ligand to study TSPO","authors":"Luminita Duma ,&nbsp;Severine Schneider ,&nbsp;Agathe Martinez ,&nbsp;Cathy Hachet ,&nbsp;Frederic Bihel ,&nbsp;Jean-Jacques Lacapere","doi":"10.1016/j.biochi.2025.01.015","DOIUrl":"10.1016/j.biochi.2025.01.015","url":null,"abstract":"<div><div>Translocator protein (TSPO, 18 kDa), previously known as peripheral-type benzodiazepine receptor, is an evolutionarily conserved membrane protein involved in various physiological processes and patho-physiological conditions. The endogeneous TSPO ligand is a polypeptide of 9 kDa, but dipeptides with biological activity have been previously synthesized and characterized. Herein, we synthesized a phenyl alanine derived ligand with a <sup>19</sup>F labelling which opens prospective for <sup>19</sup>F-MRI and potential <sup>18</sup>F-PET applications. We characterized the coexistence of two conformers that are not equally sensitive to the media used for membrane protein studies. Interaction studies with the recombinant mouse TSPO (mTSPO) in different membrane-mimicking environments are presented using <sup>19</sup>F NMR enabling structure/function characterizations. A change in the mTSPO environment from pure detergent to lipid/detergent mixture reveals different exchange rates between bound and free ligand forms. Competition experiments with the high-affinity drug ligand (<em>R</em>)-PK 11195 suggests that phenyl alanine derived ligand binds in the same protein cavity.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"233 ","pages":"Pages 14-26"},"PeriodicalIF":3.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolic adaptation mechanisms of glycogen reduction and lipid accumulation in testicular protection in Daurian ground squirrels during hibernation 达斡尔地松鼠冬眠期间睾丸保护中糖原减少和脂质积累的代谢适应机制。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-03 DOI: 10.1016/j.biochi.2025.01.014
Ming-Di Wang , Lu-Fan Li , Yu-Jing Yan , Xing-Chen Wang , Le Chen , Kai Dang , Zhe Wang , Hui-Ping Wang
{"title":"Metabolic adaptation mechanisms of glycogen reduction and lipid accumulation in testicular protection in Daurian ground squirrels during hibernation","authors":"Ming-Di Wang ,&nbsp;Lu-Fan Li ,&nbsp;Yu-Jing Yan ,&nbsp;Xing-Chen Wang ,&nbsp;Le Chen ,&nbsp;Kai Dang ,&nbsp;Zhe Wang ,&nbsp;Hui-Ping Wang","doi":"10.1016/j.biochi.2025.01.014","DOIUrl":"10.1016/j.biochi.2025.01.014","url":null,"abstract":"<div><div>The role of glycogen and lipid metabolism in the testes of Daurian ground squirrels (<em>Spermophilus dauricus</em>) during different stages of the hibernation cycle and their influence on reproductive function remain poorly understood. This study examined testicular morphology across hibernation stages and investigated potential molecular mechanisms. Results showed that: (1) Spermatocyte density was reduced in the torpor group compared to the pre-hibernation (PRE) group, suggesting a suppression of spermatogenesis during torpor. In the post-hibernation (POST) group, reduced spermatocyte density was speculated to correspond to the initial phase of spermatocyte maturation into spermatozoa. (2) Glycogen content was lower during interbout arousal (IBA), while glycogen phosphorylase (GP) activity was significantly elevated compared to the other stages. Sertoli cell density was higher in the IBA group relative to the torpor group, suggesting that elevated GP activity facilitates glycogen breakdown, providing glycolytic substrates for Sertoli cells during this phase. (3) During torpor, triglyceride and fatty acid levels, along with fatty acid synthase and acetyl-CoA carboxylase activities, remained consistent with PRE levels. These findings suggest that fatty acids are crucial for maintaining testicular reproductive function during torpor. In contrast, lipid metabolism indicators declined during the near post-hibernation (NP) and POST stages, likely supporting the rapid reactivation of reproductive processes required for the upcoming breeding season. In summary, this study highlights a dynamic interplay between lipid and glycogen metabolism across hibernation stages, with the transition from lipid-based metabolism during torpor to glycogen utilization during IBA playing a pivotal role in sustaining testicular homeostasis in Daurian ground squirrels.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"232 ","pages":"Pages 133-141"},"PeriodicalIF":3.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256160","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
Engineered IgG Fc-conjugation prolongs the half-life of florfenicol and alleviates pneumonia in mice 经改造的 IgG Fc 连接可延长氟苯尼考的半衰期并缓解小鼠肺炎。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.014
Shikun Ge , Mei Dang , Alberto Carlos Pires Dias , Xiaoying Zhang
{"title":"Engineered IgG Fc-conjugation prolongs the half-life of florfenicol and alleviates pneumonia in mice","authors":"Shikun Ge ,&nbsp;Mei Dang ,&nbsp;Alberto Carlos Pires Dias ,&nbsp;Xiaoying Zhang","doi":"10.1016/j.biochi.2024.10.014","DOIUrl":"10.1016/j.biochi.2024.10.014","url":null,"abstract":"<div><div>Small molecule drugs often exhibit short half-lives, requiring frequent administrations to maintain therapeutic concentrations over an extended period. To address this issue, the fragment crystallizable (Fc) region of IgG, known to prolong the half-life of antibodies via its interaction with the Fc neonatal receptor, was harnessed as a carrier protein to extend the half-life of a small molecule drug, florfenicol. Florfenicol, was chemically coupled to a recombinant Fc protein expressed using the eukaryotic expression system in HEK293 cells. The Fc-florfenicol conjugate exhibited a substantially prolonged half-life of from 3.8 to 9.1 h compared to unconjugated florfenicol and demonstrated excellent therapeutic properties in treating pneumonia in a mouse model. Our results, combined with the literature analysis on Fc-small molecule conjugates, show that Fc can substantially enhance the drug's half-life and suggest the potential for its use as a carrier in novel delivery systems.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 105-113"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482918","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
Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer 电阻素与乳腺癌预后、细胞迁移以及 p38 和 ERK1/2 激活之间的关系分析。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.001
Reyna L. Cuachirria-Espinoza , Alin García-Miranda , Rafael Hernández-Barragán, Dania A. Nava-Tapia, Monserrat Olea-Flores, Napoleón Navarro-Tito
{"title":"Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer","authors":"Reyna L. Cuachirria-Espinoza ,&nbsp;Alin García-Miranda ,&nbsp;Rafael Hernández-Barragán,&nbsp;Dania A. Nava-Tapia,&nbsp;Monserrat Olea-Flores,&nbsp;Napoleón Navarro-Tito","doi":"10.1016/j.biochi.2024.10.001","DOIUrl":"10.1016/j.biochi.2024.10.001","url":null,"abstract":"<div><div>Obesity increases the risk and mortality of breast cancer through dysregulated secretion of proinflammatory cytokines and tumor adipokines that induce an inflammatory breast microenvironment. Resistin is an adipokine secreted by adipocytes, immune cells, and predominantly macrophages, which contributes to cancer progression, but its molecular mechanism in cancer is not completely described. In this study, we analyzed the relationship of resistin on breast cancer prognosis and tumor progression and the effect <em>in vitro</em> of resistin on p38 and ERK1/2 activation in breast cancer cell lines. By bioinformatic analysis, we found that resistin is overexpressed in the basal subtype triple-negative breast cancer and is related to poor prognosis. In addition, we demonstrated a positive correlation between <em>RETN</em> and <em>MAPK3</em> expression in basal triple-negative breast cancer. Importantly, we found amplifications of the <em>RETN</em> gene in at least 20 % of metastatic samples from patients with breast cancer. Most samples with <em>RETN</em> amplifications metastasized to bone and showed high expression of IL-8 (<em>CXCL8</em>) and IL-6 (<em>IL6</em>). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 19-29"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382734","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
Structural extracellular matrix-mediated molecular signaling in wound repair and tissue regeneration 细胞外基质结构介导的分子信号在伤口修复和组织再生中的作用。
IF 3.3 3区 生物学
Biochimie Pub Date : 2025-02-01 DOI: 10.1016/j.biochi.2024.10.003
Sousan Cheong , Yujie Peng , Feng Lu, Yunfan He
{"title":"Structural extracellular matrix-mediated molecular signaling in wound repair and tissue regeneration","authors":"Sousan Cheong ,&nbsp;Yujie Peng ,&nbsp;Feng Lu,&nbsp;Yunfan He","doi":"10.1016/j.biochi.2024.10.003","DOIUrl":"10.1016/j.biochi.2024.10.003","url":null,"abstract":"<div><div>The extracellular matrix (ECM) is a complex, non-cellular network of molecules that offers structural support for cells and tissues. The ECM is composed of various structural components, including collagen, fibronectin, laminin, perlecan, nidogen, tenascin, and fibulin, which are capable of binding to each other and to cell-to-adhesion receptors, endowing the ECM with unique physical and biochemical properties that are essential for its function in maintaining health and managing disease. Over the past three decades, extensive research has shown that the core of the ECM can significantly impact cellular events at the molecular level. Structural modifications have also been strongly associated with tissue repair. Through interactions with cells, matrix proteins regulate critical processes such as cell proliferation and differentiation, migration, and apoptosis, essential for maintaining tissue homeostasis, formation, and regeneration. This review emphasizes the interlocking networks of ECM macromolecules and their primary roles in tissue regeneration and wound repair. Through studying ECM dynamics, researchers have discovered molecular signaling pathways that demonstrate how the ECM influences protein patterns and open up more possibilities for developing therapeutics that target the ECM to enhance wound repair and tissue regeneration.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"229 ","pages":"Pages 58-68"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382736","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
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