Biochimie最新文献

{"title":"Leptin increases lipid storage in Sertoli cells: Signaling pathways and cellular mechanisms involved","authors":"Marina Ercilia Dasso,&nbsp;Cecilia Lucia Centola,&nbsp;Florencia Nerea Tabares,&nbsp;María Noel Galardo,&nbsp;Silvina Beatriz Meroni,&nbsp;María Fernanda Riera","doi":"10.1016/j.biochi.2026.01.009","DOIUrl":"10.1016/j.biochi.2026.01.009","url":null,"abstract":"<div><div>Leptin is an adipokine with a role in male reproductive function. Sertoli cells (SCs) express leptin receptors, but leptin effects on SCs’ functions have been scarcely researched. SCs support germ cell development by providing various compounds, including transferrin and ketone bodies. Additionally, SC oxidize fatty acids (FAs) as their primary energy source and store them as triacylglycerols (TAGs) within lipid droplets (LDs), which serve as a crucial energy reserve within SCs. In the present study, we investigated whether leptin regulates the secretion and lipid storage in SCs and identified the potential signaling pathways involved. SC cultures were obtained from 20-day-old rats. The results show that leptin does not modify transferrin or 3-hydroxybutyrate secretion. However, it increases LD content and TAG levels in SCs. Leptin also augments the mRNA levels of FA transporter FAT/CD36, glycerol-3-phosphate-acyltransferase 3, and perilipin 1. We then explored the activation and the involvement of JAK/STAT3, PI3K/AKT, mTORC1/p70S6K, and PPARɣ-dependent pathways. Leptin treatment increases phosphorylated STAT3, AKT, and p70S6K levels. Also, leptin augments PPARɣ mRNA levels. In addition, we observed that Wortmannin (PI3K inhibitor), Rapamycin (mTORC1 inhibitor), and T0070907 (PPARɣ antagonist) decrease leptin-stimulated LD content, but Stattic (STAT3 inhibitor) has no effect. These results suggest that leptin regulates LD content through the activation of PI3K/AKT, mTORC1/p70S6K, and PPARɣ-dependent pathways. This study reveals that leptin increases lipid storage in SCs, a role that may help meet the seminiferous tubules' demand for FAs.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 59-69"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146042285","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":"Phase separation in regulation of gene expression: current methodological and conceptual approaches","authors":"Kalina Wegrzyn,&nbsp;Tomasz Wilanowski","doi":"10.1016/j.biochi.2026.01.003","DOIUrl":"10.1016/j.biochi.2026.01.003","url":null,"abstract":"<div><div>Phase separation underlies the formation of subcellular structures known as biomolecular condensates or membraneless organelles. In the last 15 years, a great effort has been made to characterize the biophysical properties of condensates and their role in cellular processes, including the regulation of gene expression. In this article, we provide an overview of mechanisms of phase separation in the cellular milieu, including the role of intrinsically disordered proteins, and present a repertoire of methods used to study condensate properties. Additionally, we describe recent advances regarding the role of phase separation in regulation of gene expression.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 1-17"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919149","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":"Hesperetin induces mitochondria independent apoptosis-like death in Candida albicans","authors":"Huiwon Jang ,&nbsp;Dong Gun Lee","doi":"10.1016/j.biochi.2026.01.008","DOIUrl":"10.1016/j.biochi.2026.01.008","url":null,"abstract":"<div><div>Hesperetin, a flavonoid abundantly found in citrus fruits, exhibits broad-spectrum antimicrobial activity and has been proposed as a potential alternative to conventional antifungal agents. However, its precise mode of action(s), particularly in fungal systems, remains poorly understood. This study investigated the molecular mechanism by which hesperetin exerts its antifungal effects on <em>Candida albicans</em>. Considering the reported redox-modulating properties of flavonoids, oxidative stress was evaluated by monitoring intracellular reactive oxygen species (ROS) generation. Hesperetin treatment markedly increased intracellular ROS levels, and ROS production was significantly reduced by diphenyleneiodonium (DPI), a specific inhibitor of NADPH oxidase (NOX), indicating that ROS generation originated from a NOX-dependent. Despite the elevated ROS, mitochondrial ROS release, fission and cytochrome <em>c</em> release were not observed, suggesting a mitochondria-independent pathway. Instead, cytosolic metacaspase activation was detected, accompanied by phosphatidylserine (PS) externalization, membrane disruption, and DNA fragmentation—hallmarks of apoptosis-like cell death. Collectively, these findings indicate that hesperetin induces NOX-mediated ROS production, leading to mitochondria-independent apoptosis-like death in <em>Candida albicans</em>.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 100-111"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044332","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":"Assessing the role of E451, D452, and H139 in the catalytic function of a Thermus thermophilus bacterial laccase","authors":"R. Miranda-Blancas ,&nbsp;M.C. Cardona-Echavarría ,&nbsp;G. Saab-Rincón ,&nbsp;C. Millán-Pacheco ,&nbsp;A. Landa ,&nbsp;E. Rudiño-Piñera","doi":"10.1016/j.biochi.2026.01.010","DOIUrl":"10.1016/j.biochi.2026.01.010","url":null,"abstract":"<div><div>Laccases are oxidoreductase enzymes that require four electrons and four protons for each catalytic cycle to trigger the conversion of one oxygen molecule into two water molecules. However, for bacterial laccases, including the laccase from <em>Thermus thermophilus</em> HB27 (<em>Tth</em>-MCO), the complete proton transfer pathway from the solvent-exposed surface of the protein to the trinuclear center remains unclear. This paper describes new crystallographic structures of a partially copper-occupied <em>Tth</em>-MCO, subjected to a cumulative X-ray radiation strategy to uncover the effect of the X-ray driven chemical reduction on the residues related to the enzyme's proton relay. Additionally, we constructed and analyzed single and double mutants of residues H139 and E451 to assess their effect on the kinetic parameters of <em>Tth</em>-MCO. The proper folding of the mutants was evaluated using circular dichroism, while the structural stability of the mutants was analyzed using molecular dynamics calculations based on AlphaFold 2 models. Such analysis of the structural and kinetic data obtained provides deeper insights into the amino acids involved in the proton relay mechanism of <em>Tth</em>-MCO. Considering the conservation of amino acids involved in several bacterial laccase sequences, the proposed multi-step proton relay mechanism may also exist in other bacterial laccases.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 70-79"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075136","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":"Materials and device architectures for cortisol detection: Mechanisms, measurement technologies, and clinical implications","authors":"Monali Garg ,&nbsp;Syed Gulfishan ,&nbsp;Bi Bi Zainab Mazhari ,&nbsp;Mir Waqas Alam ,&nbsp;Alis Sirohi ,&nbsp;Sandra Mathew ,&nbsp;Arun Varghese","doi":"10.1016/j.biochi.2026.01.015","DOIUrl":"10.1016/j.biochi.2026.01.015","url":null,"abstract":"<div><div>Cortisol, the primary glucocorticoid produced in response to stress, can be a chronic health risk or a protective partner. Cortisol spikes can help people survive by triggering energy mobilization, immune regulation, and neuroendocrine balance, but sustained or low cortisol levels precipitate diseases including immune dysfunction, metabolic syndrome, mood disorders, and cognitive impairment. This contribution is a review of the opposing role of cortisol, elucidating its physiological role, pathological consequences, detection techniques, regulation mechanisms, and biosynthesis. It reviews different regulatory modalities for both pharmacological and lifestyle aspects, evaluates ways of measurement, such as new wearable biosensors, and focuses on early responses of cortisol in response to factors related to pharmacological and lifestyle-based regulatory strategies and the importance of early events on responsiveness. A detailed discussion of numerous methods for the detection of cortisol is carried out. A multi-sided view of the role of cortisol in both health and disease is provided in presenting evidence from past perspectives, clinical situations, and present-day evidence based on some of the newest research.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 127-144"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095139","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":"Micronutrients shape FOXP2 activity: Mechanistic insights from retinoic acid, folic acid and pyrroloquinoline quinone","authors":"Mande Goldfein,&nbsp;Sylvia Fanucchi","doi":"10.1016/j.biochi.2026.01.016","DOIUrl":"10.1016/j.biochi.2026.01.016","url":null,"abstract":"<div><div>FOXP2 is a neurodevelopmental transcription factor that regulates genes essential for neuronal differentiation, synaptic connectivity, and speech and language. Here, we show that the small neuroactive molecules retinoic acid (RA), folic acid (FA), and pyrroloquinoline quinone (PQQ), can associate with the FOXP2 forkhead domain (FHD) and are accompanied by ligand-specific changes in protein conformation, DNA binding behaviour and transcriptional output. Through a combination of biochemical assays, fluorescence anisotropy, cellular reporter analyses, and molecular simulations, we reveal that each ligand engages FOXP2 in a structurally distinct manner that translates into specific functional outcomes. RA and FA promote a more flexible, open conformation of the DNA-bound FHD, enhancing DNA affinity and transcriptional activation, while PQQ stabilises a compact, rigid state associated with reduced transcription. These findings support the possibility that nutrient-derived ligands can fine-tune transcription factor dynamics and function through direct or context-dependent interactions, with the strongest evidence observed for RA, suggesting a mechanism by which metabolic and nutritional cues may directly influence neurodevelopmental gene regulation. This work reveals a previously unrecognised mode of transcription factor modulation by micronutrients, suggesting that dietary components may directly influence the structural and hence regulatory properties of FOXP2. This work opens new avenues for understanding nutrient-responsive transcriptional networks in the brain.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 86-99"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095118","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":"Human CELA1 has pancreatic elastase-like activity","authors":"Deepti Jamwal ,&nbsp;Prince Kumar ,&nbsp;Kunal Meena ,&nbsp;Vikash Yadav ,&nbsp;Rajesh Kumar ,&nbsp;Nidhi Adlakha ,&nbsp;Supratik Das","doi":"10.1016/j.biochi.2026.01.004","DOIUrl":"10.1016/j.biochi.2026.01.004","url":null,"abstract":"<div><div>CELA3A and CELA3B are the primary elastases secreted by the human pancreas that are digestive enzymes and are markers for pancreatic exocrine insufficiency. CELA1, another family member, is not expressed in the human pancreas but has been detected in the mouse lung and human keratinocytes. However, the enzymatic activity and mechanism of function of human CELA1 has not been previously demonstrated. Here, we show using purified, recombinant pro-hCELA1, that it is activated by trypsin and has pancreatic elastase-like activity. We show that pro-hCELA1 cleavage by trypsin is blocked by aprotinin. We have determined the enzyme kinetics of the active fraction of recombinant hCELA1 and show that it follows steady-state kinetics with a higher substrate affinity than commercial porcine pancreatic elastase.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 18-20"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954288","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":"The shifting sands of venom: Divergent blood clotting factor activation pathways and differential Factor Va co-factor dependence for the venoms of Middle Eastern desert vipers (Eristicophis and Pseudocerastes species)","authors":"Patrick S. Champagne ,&nbsp;Lorenzo Seneci ,&nbsp;Behzad Fathinia ,&nbsp;Parviz Ghezellou ,&nbsp;Syed A. Ali ,&nbsp;Bryan G. Fry","doi":"10.1016/j.biochi.2026.01.011","DOIUrl":"10.1016/j.biochi.2026.01.011","url":null,"abstract":"<div><div>Desert vipers (<em>Eristicophis</em> and <em>Pseudocerastes</em>) employ diverse procoagulant strategies despite their close phylogenetic relationships, yet the biochemical mechanisms underlying the variations in their coagulotoxic activities remain poorly understood. We conducted comprehensive coagulation factor activation studies across all four species in the clade: <em>Eristicophis macmahoni</em> (Ema), <em>Pseudocerastes fieldi</em> (Pfi), <em>P. persicus</em> (Ppe), and <em>P. urarachnoides</em> (Pur). Plasma clotting assays revealed extreme variation in coagulation speed (17.3–376.1 s), with <em>E. macmahoni</em> and <em>P. urarachnoides</em> emerging as rapid coagulators. Fluorometric zymogen activation studies demonstrated that all species require Factor Va as a cofactor for optimal activity, with species-specific preferences for either the endogenous form of Factor Va produced by circulating thrombin or the FVa produced by the venom directly cleaving Factor V. This suggests that the venoms cleave FV at sites distinct from the cleavage site utilised by endogenous thrombin. The species had dramatically distinct patterns of factor activation: Factor XII was most strongly activated factor, and had a venom rank order of Pur ≫ Ema &gt; Pfi = Ppe; Factor X was the next most potently activated factor, with a venom rank order of Ema = Pfi &gt; Pur &gt; Ppe; followed by Factor VII Pfi &gt; Ppe &gt; Ema = Pur; and prothrombin (Factor II) Ema &gt; Pur, with activation by Pfi or Ppe not detectable. None of the venoms activated Factor XI. Notably, despite being suggested as a bird-specialist, <em>P. urarachnoides</em> exhibiting the highest Factor XII activation capacity is significant as avians have secondarily lost FXII as a component in their coagulation cascade. As such, the potent activation of FXII suggest non-avian prey species such as lizards or small rodents make up a significant proportion of this species diet. Antivenom efficacy studies revealed species-specific patterns, with the VINS Jorven antivenom showing superior neutralization against <em>P. urarachnoides</em> and <em>Eristicophis macmahoni</em> relative to the Inosan Inoserp-MENA antivenom and National Antivenom and Vaccine Production Centre of Saudi Arabia antivenom. These toxicology findings reveal that despite morphological similarity and shared ecological niches, desert vipers have evolved fundamentally distinct coagulotoxicity approaches to prey immobilization. These species-specific pathophysiological profiles have important clinical implications for antivenom development and bite treatment protocols in endemic regions.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 112-126"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088303","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":"ShortCut RNase III is capable of digesting single mRNA transcripts into < 10 nucleotide products","authors":"Kyle J. Tynan,&nbsp;Mark S. Lowenthal,&nbsp;Karndeep Singh,&nbsp;Trina Mouchahoir,&nbsp;Daniel Hunter,&nbsp;Karen W. Phinney","doi":"10.1016/j.biochi.2026.01.012","DOIUrl":"10.1016/j.biochi.2026.01.012","url":null,"abstract":"<div><div>RNase III is a dsRNA-specific ribonuclease that has been used to enzymatically digest dsRNA impurities generated during <em>in vitro</em> transcription. Here, we demonstrate that ShortCut RNase III, a recombinant version of <em>E. coli</em> RNase III fused with maltose binding protein which is reported to digest dsRNA to 18–25 base pair fragments, can also degrade single-stranded Cas9 mRNA to fragments as short as 9 nucleotides. These findings indicate that ShortCut RNase III exhibits unexpected activity beyond canonical dsRNA cleavage, raising concerns about its suitability for removing dsRNA impurities in mRNA manufacturing.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 80-85"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088378","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":"Relationship between structure and function of the NADH oxidase from Lactobacillus brevis","authors":"Mathieu Dondelinger,&nbsp;Marylène S. Vandevenne,&nbsp;Frédéric Kerff,&nbsp;Moreno Galleni","doi":"10.1016/j.biochi.2025.12.013","DOIUrl":"10.1016/j.biochi.2025.12.013","url":null,"abstract":"<div><div>Water-producing NADH oxidases catalyse the oxidation of NADH by molecular oxygen to generate NAD⁺ and water. These enzymes require FAD as cofactor to carry out their enzymatic activity and contribute to bacterial protection against oxidative stress. They have received considerable attention since their NAD⁺ recycling activity could make them candidates of choice for various industrial oxidoreductive processes. However, most of these enzymes are produced in recombinant hosts (e.g., <em>E. coli</em>) as apoenzymes and therefore require activation by incubation with FAD.</div><div>In this study, we describe the characterization of the NADH oxidase from <em>Lactobacillus brevis</em> (LbNOX), a homodimeric flavoenzyme containing one non-covalently bound FAD molecule per monomer. In this paper, we show that the production, purification and formulation of LbNOX result in a heterogeneous enzyme solution. The active dimeric form is pH dependent and correlates with the presence of FAD. We also performed a comprehensive bioinformatic analysis of the LbNOX structure, which highlights crucial residues for pH-dependent dimerisation and shows that FAD is tightly bound at the dimerisation interface.</div><div>This structural and functional characterization is crucial for a complete understanding of the enzyme's activation mechanism and will support the development of a robust and reproducible protocol for the production, purification and formulation of a fully active and homogeneous enzyme solution. More broadly, this work will contribute to the development of NADH oxidases based industrial applications and their FAD-dependent activation mechanism.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 145-159"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004603","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}