Biochimica et biophysica acta. General subjects最新文献

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Histone acetylation and BRD4 binding are associated with induction of TNF mRNA expression by temporal high-glucose exposure and subsequent low-glucose culture in juvenile macrophage-like THP-1 cells 在幼年巨噬细胞样THP-1细胞中,组蛋白乙酰化和BRD4结合与时间性高糖暴露和随后的低糖培养诱导TNF mRNA表达相关。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-13 DOI: 10.1016/j.bbagen.2025.130759
Chihiro Imai , Toshinao Goda , Kazuki Mochizuki
{"title":"Histone acetylation and BRD4 binding are associated with induction of TNF mRNA expression by temporal high-glucose exposure and subsequent low-glucose culture in juvenile macrophage-like THP-1 cells","authors":"Chihiro Imai ,&nbsp;Toshinao Goda ,&nbsp;Kazuki Mochizuki","doi":"10.1016/j.bbagen.2025.130759","DOIUrl":"10.1016/j.bbagen.2025.130759","url":null,"abstract":"<div><h3>Background</h3><div>Postprandial hyperglycemia induces expression of inflammatory cytokines including tumor necrosis factor (TNF), which promotes the onset of type 2 diabetes and cardiovascular diseases. In this study, we investigated whether a transient high-glucose culture enhanced sustained expression of <em>TNF</em>, or whether the induction is associated with histone acetylation, and bromodomain protein containing protein 4 (BRD4), which binds acetylated histone, in human juvenile macrophage-like THP-1 cells.</div></div><div><h3>Methods</h3><div>THP-1 cells were cultured in medium with high-glucose in the presence or absence of (+)-JQ1, an inhibitor of bromodomain and extra-terminal domain family, for 24 h (day 0). Thereafter, the cells were returned to a low-glucose medium without (+)-JQ1 and cultured for 2 or 4 days and samples were collected. mRNA expression of inflammation genes, and histone H3 K9/14 acetylation and binding of BRD4 and RNA polymerase II around the <em>TNF</em> gene were measured by RT-qPCR and chromatin immunoprecipitation, respectively.</div></div><div><h3>Results</h3><div><em>TNF</em> mRNA levels, histone H3 K9/14 acetylation, and bindings of BRD4 and RNA polymerase II to the <em>TNF</em> gene were higher in cells exposed to high-glucose culture for 24 h and subsequently cultured in low-glucose medium for 2–4 days, compared with cells cultured in a low-glucose medium. The addition of (+)-JQ1 to the high-glucose medium for 24 h reduced histone H3 K9/14 acetylation, and BRD4 and RNA polymerase II bindings around <em>TNF</em> gene, and the mRNA levels.</div></div><div><h3>Conclusions</h3><div>Histone H3 K9/14 acetylation and BRD4 binding are associated with the sustained expression of <em>TNF</em> mRNA induced by temporal high-glucose exposure in juvenile macrophage-like THP-1 cells.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130759"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999478","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
Roles of acyl carrier proteins in ladderane fatty acid producing-organisms 酰基载体蛋白在脂酰脂肪酸产生生物中的作用。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-11 DOI: 10.1016/j.bbagen.2025.130763
Tamara Schmidt , Chang Ding , Tadeo Moreno-Chicano , Paola Granatino , Jolanta Nickel , Sabine Zimmermann , Lorenz Adrian , Andreas Dietl , Thomas Barends
{"title":"Roles of acyl carrier proteins in ladderane fatty acid producing-organisms","authors":"Tamara Schmidt ,&nbsp;Chang Ding ,&nbsp;Tadeo Moreno-Chicano ,&nbsp;Paola Granatino ,&nbsp;Jolanta Nickel ,&nbsp;Sabine Zimmermann ,&nbsp;Lorenz Adrian ,&nbsp;Andreas Dietl ,&nbsp;Thomas Barends","doi":"10.1016/j.bbagen.2025.130763","DOIUrl":"10.1016/j.bbagen.2025.130763","url":null,"abstract":"<div><div>Ladderanes are highly strained hydrocarbons consisting of two or more linearly concatenated cyclobutane rings. Strikingly, ladderane moieties are part of unique fatty acids and fatty alcohols that are exclusively found in the membrane lipids of anaerobic ammonium-oxidizing (anammox) bacteria. These bacteria express a distinctive gene cluster (cluster I) that has been suggested to be responsible for ladderane fatty acid (FA) biosynthesis in addition to a cluster likely involved in canonical FA biosynthesis (cluster III). In the anammox organism <em>Kuenenia stuttgartiensis,</em> cluster I encodes a unique acyl carrier protein (amxACP), whereas the ACP encoded by cluster III (KsACPII) was suggested to be involved in the production of canonical fatty acids. Here we present targeted isotope labeling studies using <sup>13</sup>C-malonyl-ACPs to distinguish the roles of these ACPs. While <em>in-vitro</em> <sup>13</sup>C incorporation into ladderane FAs was not observed, we show that KsACPII indeed functions in palmitate biosynthesis in the anammox organism <em>Kuenenia stuttgartiensis.</em> We present an experimental framework for continuing studies into fatty acid biosynthesis in anammox- and similar organisms.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130763"},"PeriodicalIF":2.8,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976785","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
Elucidating the roles of voltage sensors in NaV1.9 activation and inactivation through a spider toxin 通过蜘蛛毒素阐明电压传感器在NaV1.9激活和失活中的作用。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-10 DOI: 10.1016/j.bbagen.2025.130762
Shuijiao Peng , Minzhi Chen , Meijing Wu , Zhonghua Liu , Dongfang Tang , Xi Zhou
{"title":"Elucidating the roles of voltage sensors in NaV1.9 activation and inactivation through a spider toxin","authors":"Shuijiao Peng ,&nbsp;Minzhi Chen ,&nbsp;Meijing Wu ,&nbsp;Zhonghua Liu ,&nbsp;Dongfang Tang ,&nbsp;Xi Zhou","doi":"10.1016/j.bbagen.2025.130762","DOIUrl":"10.1016/j.bbagen.2025.130762","url":null,"abstract":"<div><div>The gating process of voltage-gated sodium (Na<sub>V</sub>) channels is extraordinary intrinsic and involves numerous factors, such as voltage-sensing domain (VSD), the N-terminus and C-terminus, and the auxiliary subunits. To date, the gating mechanism of Na<sub>V</sub> channel has not been clearly elucidated. Na<sub>V</sub>1.9 has garnered significant attention due to its slow gating kinetics. Due to the challenges of Na<sub>V</sub>1.9 heterologous expression, research on its gating mechanism is relatively limited. Whether there are any differences in the functions of the four VSDs in Na<sub>V</sub>1.9 compared to those in other subtypes remains an open question. Here, we employed the established chimera method to transplant the S3b-S4 motif from the VSDIV of the toxin-sensitive donor channel (Na<sub>V</sub>1.9) into the receptor channel (Na<sub>V</sub>1.9/1.8 DIV S3b-S4 chimera). This modification imparted animal toxin sensitivity to the other three VSDs. Our results demonstrate that all four VSDs of Na<sub>V</sub>1.9 are involved in channel opening, VSDIII and VSDIV are primarily involved in regulating fast inactivation, and VSDII also regulates the steady-state inactivation of channels. These findings provide a new insight into the gating mechanism of Na<sub>V</sub>1.9.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130762"},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969436","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
Conformational switches in human RNA binding proteins involved in neurodegeneration 参与神经退行性变的人类RNA结合蛋白的构象开关。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-10 DOI: 10.1016/j.bbagen.2025.130760
Sonali Chatterjee , Atanu Maity , Ranjit Prasad Bahadur
{"title":"Conformational switches in human RNA binding proteins involved in neurodegeneration","authors":"Sonali Chatterjee ,&nbsp;Atanu Maity ,&nbsp;Ranjit Prasad Bahadur","doi":"10.1016/j.bbagen.2025.130760","DOIUrl":"10.1016/j.bbagen.2025.130760","url":null,"abstract":"<div><div>Conformational switching in RNA binding proteins (RBPs) is crucial for regulation of RNA processing and transport. Dysregulation or mutations in RBPs and broad RNA processing abnormalities are related to many human diseases including neurodegenerative disorders. Here, we review the role of protein-RNA conformational switches in RBP-RNA complexes. RBP-RNA complexes exhibit wide range of conformational switching depending on the RNA molecule and its ability to induce conformational changes in its partner RBP. We categorize the conformational switches into three groups: rigid body, semi-flexible and full flexible. We also investigate conformational switches in large cellular assemblies including ribosome, spliceosome and RISC complexes. In addition, the role of intrinsic disorder in RBP-RNA conformational switches is discussed. We have also discussed the effect of different disease-causing mutations on conformational switching of proteins associated with neurodegenerative diseases. We believe that this study will enhance our understanding on the role of protein-RNA conformational switches. Furthermore, the availability of a large number of atomic structures of RBP-RNA complexes in near future would facilitate to create a complete repertoire of human RBP-RNA conformational switches.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130760"},"PeriodicalIF":2.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969430","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 three-dimensional co-culture model for studying exosome-mediated cell interactions in glioblastoma 研究胶质母细胞瘤中外泌体介导的细胞相互作用的新型三维共培养模型。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-08 DOI: 10.1016/j.bbagen.2024.130752
Kaishu Li , Siyuan Du , Haichao Li , Zhaohui Li , Qihui Zhu , Qian Peng , Baojian Liao , Ling Qi
{"title":"A novel three-dimensional co-culture model for studying exosome-mediated cell interactions in glioblastoma","authors":"Kaishu Li ,&nbsp;Siyuan Du ,&nbsp;Haichao Li ,&nbsp;Zhaohui Li ,&nbsp;Qihui Zhu ,&nbsp;Qian Peng ,&nbsp;Baojian Liao ,&nbsp;Ling Qi","doi":"10.1016/j.bbagen.2024.130752","DOIUrl":"10.1016/j.bbagen.2024.130752","url":null,"abstract":"<div><div>Three-dimensional(3D) cell culture systems provide a larger space for cell proliferation, which is crucial for simulating cellular behavior and drug responses in the tumor microenvironment. In this study, we developed a novel 3D co-culture system for cell interactions, utilizing a commercialized bioreactor-microcarrier system. Mesenchymal stem cells (MSCs) were extracted via enzymatic digestion, and markers CD105 and CD31 were identified. Cell growth was observed using AO and immunofluorescence staining. No significant differences in Ki67 and GFAP expression were found between 2D and 3D cultures, though the 3D system offered more space for proliferation and reduced contact inhibition. Therefore, this 3D culture system may represent the tumor microenvironment more accurately than 2D cultures and will facilitate the investigation of the characteristics and functions of exosomes derived from this system. Exosomes are nanoscale vesicles that mediate intercellular communication by transferring molecules such as miRNAs between cells. Exosomes from 3D cultures were collected via ultra-high-speed centrifugation and characterized using nano-flow cytometry, transmission electron microscopy, and western blotting for markers CD9, Alix, and TSG101. PKH26 staining revealed peak exosome uptake by tumor cells at 24 h and complete metabolism by 72 h. Exosomes from 3D cultures inhibited GBM cell proliferation, migration, and invasion. Lastly, miRNA sequencing of exosomes was performed. This study emphasizes the importance of creating 3D co-culture systems to advance cancer research and offers a helpful tool for studying the complex cell interaction environment of GBM and other malignancies.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130752"},"PeriodicalIF":2.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963664","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
Growth inhibition and toxicity assessments of cis-3,4-diaryl-α-methylene-γ-butyrolactams in cultured human renal cancer cells and zebrafish embryos 顺式-3,4-二芳基-α-亚甲基-γ-丁内酰胺在培养的人肾癌细胞和斑马鱼胚胎中的生长抑制和毒性评价。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-07 DOI: 10.1016/j.bbagen.2025.130761
Adam Shih-Yuan Lee , Ta-Hsien Lin , Yen-Yu Liu , Yun-Hsin Wang , Shu-Chun Cheng , Tao-Sheng Li , Chiao-Yin Sun , Yau-Hung Chen
{"title":"Growth inhibition and toxicity assessments of cis-3,4-diaryl-α-methylene-γ-butyrolactams in cultured human renal cancer cells and zebrafish embryos","authors":"Adam Shih-Yuan Lee ,&nbsp;Ta-Hsien Lin ,&nbsp;Yen-Yu Liu ,&nbsp;Yun-Hsin Wang ,&nbsp;Shu-Chun Cheng ,&nbsp;Tao-Sheng Li ,&nbsp;Chiao-Yin Sun ,&nbsp;Yau-Hung Chen","doi":"10.1016/j.bbagen.2025.130761","DOIUrl":"10.1016/j.bbagen.2025.130761","url":null,"abstract":"<div><div>This study aimed to compare and evaluate the growth inhibition effects of eight previously synthesized compounds, <em>cis</em>-3,4-diaryl-α-methylene-γ-butyrolactams (compounds 1–8), on two human renal carcinoma cell (RCC) lines: CRL-1932 (rapid growth) and HTB-44 (slow growth). MTT assays and flow cytometry were conducted, revealing that compounds 5 and 6 had the potential to induce cell death in the slow-growing RCC cells (HTB-44), while compound 8 demonstrated effectiveness in both RCC lines (HTB-44 and CRL-1932). Additionally, a non-transformed HEK293 cell line and a transgenic zebrafish with a green fluorescent kidney Tg(<em>wt1b</em>:<em>egfp</em>) were used to assess the toxicities of compounds 5, 6, and 8. The findings suggested that compound 8 was relatively non-toxic compared to the others. Western blot analysis indicated that compounds 5, 6, and 8 may interact with the P53/mTOR pathways. Based on these results, we concluded that compound 8 exhibits RCC growth inhibition properties and has lower toxicity, making it a candidate for further investigation in mammalian models.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130761"},"PeriodicalIF":2.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943627","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
Chloroplast arrangement in finger millet under low-temperature conditions 低温条件下谷子叶绿体排列。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-06 DOI: 10.1016/j.bbagen.2025.130757
Eri Maai , Mikiko Kojima , Yumiko Takebayashi , Hitoshi Sakakibara
{"title":"Chloroplast arrangement in finger millet under low-temperature conditions","authors":"Eri Maai ,&nbsp;Mikiko Kojima ,&nbsp;Yumiko Takebayashi ,&nbsp;Hitoshi Sakakibara","doi":"10.1016/j.bbagen.2025.130757","DOIUrl":"10.1016/j.bbagen.2025.130757","url":null,"abstract":"<div><h3>Background</h3><div>Finger millet, a C<sub>4</sub> plant with mesophyll and bundle sheath cells, has been cultivated at high altitudes in the Himalayas owing to its adaptability to stressful environments. Under environmental stresses such as high light and drought, finger millet mesophyll chloroplasts move toward the bundle sheath, a phenomenon known as aggregative arrangement.</div></div><div><h3>Methods</h3><div>To investigate the effect of low temperatures on mesophyll chloroplast arrangement in finger millet, we conducted microscopic observations and photochemical measurements using leaves treated at different temperatures in light or darkness, with or without pharmacological inhibitors. Abscisic acid (ABA) content was also quantified.</div></div><div><h3>Results</h3><div>Chloroplast aggregative arrangement was induced at 5 °C in a light- and actin-dependent manner. This response required a lower intensity of blue light than that previously observed at moderate temperatures. Low temperature significantly reduced the maximum quantum efficiency of photosystem II and increased leaf ABA content in the light. Conversely, in the absence of blue light at low temperatures or under actin-inhibited conditions, mesophyll chloroplasts exhibited a doughnut-like arrangement, characterized by a distribution away from the bundle sheath side.</div></div><div><h3>Conclusions</h3><div>In finger millet, mesophyll chloroplasts move toward the bundle sheath through a blue light and actin-based mechanism at low temperatures. The doughnut-like arrangement appears to be a contingent phenomenon that manifests when the dispersion of mesophyll chloroplasts toward the bundle sheath is impeded.</div></div><div><h3>General significance</h3><div>The aggregative arrangement is a response to various environmental stresses, including low temperatures, and may be advantageous for finger millet seedlings in mitigating photoinhibition during cool mornings.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130757"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943626","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
Applications of MicroED in structural biology and structure-based drug discovery MicroED在结构生物学和基于结构的药物发现中的应用。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-04 DOI: 10.1016/j.bbagen.2025.130758
Salma Mirza , Malik Shoaib Ahmad
{"title":"Applications of MicroED in structural biology and structure-based drug discovery","authors":"Salma Mirza ,&nbsp;Malik Shoaib Ahmad","doi":"10.1016/j.bbagen.2025.130758","DOIUrl":"10.1016/j.bbagen.2025.130758","url":null,"abstract":"<div><div>Microcrystal electron diffraction (MicroED) is an emerging method for the structure determination of proteins and peptides, enzyme-inhibitor complexes. Several structures of biomolecules, including lysozyme, proteinase K, adenosine receptor A2A, insulin, xylanase, thermolysin, DNA, and Granulovirus occlusion bodies, have been successfully determined through MicroED. As MicroED uses very small crystals for structure determination, therefore, it has several advantages over conventional X-ray diffraction methods. In this review article, we discussed the most recent developments in the field of MicroED and its applications for the structural determination of different types of peptides, proteins, enzymes, DNA, and enzyme-inhibitor-complexed structures.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130758"},"PeriodicalIF":2.8,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943628","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
Androgens induce renal synthesis of urinary lipocalin-family protein, a potential inter-sexual transmitter in viviparous rockfish 雄激素诱导肾合成尿脂钙素家族蛋白,这是一种潜在的胎生岩鱼的两性间传递素。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-04 DOI: 10.1016/j.bbagen.2025.130756
Yo Yamaguchi , Jun Nagata , Takuma Kawasaki , Takashi Todo , Naoshi Hiramatsu
{"title":"Androgens induce renal synthesis of urinary lipocalin-family protein, a potential inter-sexual transmitter in viviparous rockfish","authors":"Yo Yamaguchi ,&nbsp;Jun Nagata ,&nbsp;Takuma Kawasaki ,&nbsp;Takashi Todo ,&nbsp;Naoshi Hiramatsu","doi":"10.1016/j.bbagen.2025.130756","DOIUrl":"10.1016/j.bbagen.2025.130756","url":null,"abstract":"<div><div>In viviparous black rockfish (<em>Sebastes schlegelii</em>), the kidney of reproductive-phase males actively produces lipocalin-type prostaglandin D<sub>2</sub> synthase homolog (LPGDSh) protein, which is presumably involved in inter-sexual communication when emitted in the urine. The present study was undertaken to discover whether androgens and their nuclear receptors (Ars) are engaged in regulation of renal LPGDSh protein synthesis in black rockfish. Quantitative real-time polymerase chain reaction, in conjunction with immunohistochemistry and highly sensitive enzyme-linked immunosorbent assay, revealed that intra-abdominal administration of a synthetic androgen, 17α-methyltestosterone (MT), to juvenile black rockfish induced their renal expression of LPGDSh transcript and protein. In situ hybridization visualized <em>arα</em> and <em>arβ</em> transcripts in the renal tubules of mature males during the copulation season, where they were co-localized with LPGDSh protein. Androgens, such as 11β-hydroxytestosterone, MT, dihydrotestosterone, 11-ketotestosterone (11KT), testosterone, and androstenedione transactivated a luciferase reporter vector containing four repeats of a consensus androgen response element (ARE) in the presence of black rockfish Ars (either Arα or Arβ), with differences in ligand-preference and dose-response profiles being observed between the two Ars. In the presence of 11KT, the Ars transactivated a reporter vector containing the proximal 5′-flanking region of an LPGDSh gene in luciferase reporter assays. The region between 2100 bp and 1110 bp upstream from the start codon of the LPGDSh gene, wherein many ARE-like motifs are densely distributed, was imperative for the androgenic transactivation response of the 5′-flanking region. Collectively, these observations verify that renal synthesis of LPGDSh protein is upregulated by androgens.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 3","pages":"Article 130756"},"PeriodicalIF":2.8,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963665","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
TOE1 deadenylase inhibits gastric cancer cell proliferation by regulating cell cycle progression TOE1 deadenylase通过调控细胞周期进程抑制胃癌细胞增殖。
IF 2.8 3区 生物学
Biochimica et biophysica acta. General subjects Pub Date : 2025-01-01 DOI: 10.1016/j.bbagen.2024.130736
Xiao-Lin Sun , Huan-Xi Song , Jia-Hui Li, Yi-Jin Liu, Xin-Ya Wang, Li-Na Zhang
{"title":"TOE1 deadenylase inhibits gastric cancer cell proliferation by regulating cell cycle progression","authors":"Xiao-Lin Sun ,&nbsp;Huan-Xi Song ,&nbsp;Jia-Hui Li,&nbsp;Yi-Jin Liu,&nbsp;Xin-Ya Wang,&nbsp;Li-Na Zhang","doi":"10.1016/j.bbagen.2024.130736","DOIUrl":"10.1016/j.bbagen.2024.130736","url":null,"abstract":"<div><div>TOE1, also known as hCaf1z, belongs to the DEDD superfamily of deadenylases and a newly identified isoenzyme of hCaf1 deadenylases. Previous research has demonstrated that TOE1 has deadenylase activity, which can catalyze the degradation of poly(A) substrates and interact with hCcr4d to form the unconventional human Ccr4-Caf1 deadenylase complex. Our recent research indicates that hCaf1a and hCaf1b isoenzymes, highly expressed in gastric cancer, promote gastric cancer cell proliferation and tumorigenicity <em>via</em> modulating cell cycle progression. However, no studies have yet explored the relationship between TOE1 deadenylase and tumor development. In our study, we systematically investigated the functions and mechanisms of TOE1 in gastric cancer progression. Our findings revealed that overexpression of TOE1 inhibited gastric cancer cell proliferation, invasion and migration, promoted cell apoptosis, and led to cell cycle arrest in G0/G1 phase, while TOE1 knockdown had the opposite biological effects on these processes in gastric cancer cells. Further results indicated that TOE1 suppressed gastric cancer progression by inhibiting EMT process and MMPs expression. Moreover, our study clarified that TOE1 blocked gastric cancer cell cycle progression by up-regulating the expression level of the key cell cycle factors p21 and p53 through different regulatory mechanisms. Specifically, TOE1 up-regulated p53 expression by enhancing p53 promoter activity, and up-regulated p21 expression by enhancing <em>p21</em> mRNA stability. Collectively, our findings first contribute to further elucidating the molecular mechanisms by which TOE1 participates in the regulation of gastric cancer progression, and are expected to provide a theoretical basis for diagnosis and targeted treatment of gastric cancer.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 1","pages":"Article 130736"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805925","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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