The FEBS journal最新文献

{"title":"Protection of beta cells against cytokine-induced apoptosis by the gut microbial metabolite butyrate.","authors":"Kasper Suhr Jørgensen, Signe Schultz Pedersen, Siv Annegrethe Hjorth, Nils Billestrup, Michala Prause","doi":"10.1111/febs.17334","DOIUrl":"https://doi.org/10.1111/febs.17334","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is characterized by immune cell infiltration in the islets of Langerhans, leading to the destruction of insulin-producing beta cells. This destruction is driven by secreted cytokines and cytotoxic T cells inducing apoptosis in beta cells. Butyrate, a metabolite produced by the gut microbiota, has been shown to have various health benefits, including anti-inflammatory and anti-diabetic effects. In this study, we investigated the potential protective effects of butyrate on cytokine-induced apoptosis in beta cells and explored the underlying mechanisms. Insulin-secreting INS-1E cells and isolated mouse islets were treated with interleukin-1beta (IL-1β) or a combination of IL-1β and interferon-gamma (IFN-γ) in the presence or absence of butyrate. We analyzed apoptosis, nitric oxide (NO) levels, expression of stress-related genes, and immune cell migration. Our results demonstrated that butyrate significantly attenuated cytokine-induced apoptosis in both INS-1E cells and mouse islets, accompanied by a reduction in NO levels. Butyrate also decreased the expression of endoplasmic reticulum (ER) stress markers such as Chop, phosphorylated eIF2α and Atf4, as well as some pro-apoptotic genes including Dp5 and Puma. Butyrate reduced the cytokine-induced expression of the chemokine genes Cxcl1 and Cxcl10 in mouse islets, as well as the chemotactic activity of THP-1 monocytes toward conditioned media from IL-1β-exposed islets. In conclusion, these findings indicate that butyrate protects beta cells from cytokine-induced apoptosis and ER stress, suggesting its potential as a therapeutic agent to prevent beta cell destruction in T1D.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome-based analysis of the molecular mechanism of recombinant protein expression in Periplaneta americana cells.","authors":"Chenjing Ma, Xin Zhang, Xian Li, Weifeng Ding, Hang Chen, Ying Feng","doi":"10.1111/febs.17331","DOIUrl":"https://doi.org/10.1111/febs.17331","url":null,"abstract":"<p><p>The Insect Cell-Baculovirus Expression Vector System (IC-BEVS) is widely used for the generation of a variety of gene products, including proteins, vaccines, and gene therapy vectors; however, it has some limitations, including a constrained host range and low protein yields. In a previous study, we established the RIRI-PA1 cell line, which was derived from Periplaneta americana. This cell line is susceptible to Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infection, which results in a higher yield production of recombinant protein within a short post-infection period of 24-48 h compared to the commonly used engineered cell line Sf21. To elucidate the basis for this phenomenon, we used RNA sequencing and transcriptome analysis of RIRI-PA1 and Sf21 cells infected with AcMNPV-GFP at 24, 72, and 168 h post-infection. Differentially expressed genes (DEGs) were identified in both cell lines. GO, eggNOG, and KEGG annotation analyses were used to identify DEGs and select candidate genes that could regulate recombinant protein expression. The results indicated a significant link between ribosomal pathway regulation and recombinant protein expression. After 24 h of AcMNPV-GFP infection, relatively high levels of protein were produced in RIRI-PA1 cells compared to Sf21 cells, which exhibited lesser enrichment of ribosomal protein-related DEGs (7 : 12). Moreover, a correlation was observed in the gene expression patterns between AcMNPV-GFP infection and recombinant protein synthesis, including genes associated with the ribosome, Toll and Imd signaling, and the cytochrome P450 pathway. Overall, our findings suggested that the ribosomal pathway might be more involved in regulation of protein expression during the early stages of RIRI-PA1 infection. The mechanisms underlying this process could have potential future applications in engineering cell modifications to reduce production time for recombinant proteins and to promote the use of IC-BEVS.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous reversal of small molecule-induced mitochondrial uncoupling: the case of anilinothiophenes.","authors":"Roman S Kirsanov, Ljudmila S Khailova, Vladimir S Krasnov, Alexander M Firsov, Konstantin G Lyamzaev, Alisa A Panteleeva, Lyudmila B Popova, Pavel A Nazarov, Vadim N Tashlitsky, Galina A Korshunova, Elena A Kotova, Yuri N Antonenko","doi":"10.1111/febs.17329","DOIUrl":"https://doi.org/10.1111/febs.17329","url":null,"abstract":"<p><p>Tissue specificity can render mitochondrial uncouplers more promising as leading compounds for creating drugs against serious diseases. In search of tissue-specific uncouplers, we address anilinothiophenes as possible glutathione-S-transferase substrates (GST). Earlier, 'cyclic' uncoupling activity was reported for 5-bromo-N-(4-chlorophenyl)-3,4-dinitro-2-thiophenamine (BDCT) in isolated rat liver mitochondria (RLM). The mechanism by which BDCT induced two-phase changes in mitochondrial respiration (stimulation followed by deceleration) was unknown. To clarify this issue, we synthesized BDCT and its two analogues. Among these, 5-bromo-3,4-dinitro-N-(4-nitrophenyl)-2-thiophenamine (BDNT) appeared to be the most effective as a mitochondrial uncoupler, decreasing membrane potential and stimulating respiration at submicromolar concentrations. Importantly, BDNT exerted two-phase changes in both mitochondrial membrane potential and respiration rate of RLM, which were enhanced by the addition of glutathione (GSH) but inhibited by the compounds capable of GSH depleting, such as 1-chloro-2,4-dinitrobenzene (CDNB). By contrast, the phase of recoupling was not observed in rat heart mitochondria (RHM). Remarkably, BDNT elicited mitochondrial depolarization in primary human fibroblasts but not in cultured human liver (HepG2) cells. By detecting proton-selective electrical current through planar bilayer lipid membranes, we demonstrated the ability of BDCT and BDNT to transfer protons across membranes. BDNT proved to be an anionic protonophore with a pK_a of 7.38. By using LC-MS and capillary electrophoresis, we directly showed the formation of BDNT conjugates with GSH upon incubation with RLM but not RHM. Therefore, we hypothesize that GST is involved in the disappearance of the anilinothiophene uncoupling activity in RLM, ensuring the tissue-specific behavior of the uncoupler.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction with the cysteine-free protein HAX1 expands the substrate specificity and function of MIA40 beyond protein oxidation.","authors":"Robin Alexander Rothemann, Dylan Stobbe, Michaela Nicole Hoehne-Wiechmann, Lena Maria Murschall, Esra Peker, Lara Katharina Knaup, Julia Racho, Markus Habich, Sarah Gerlich, Kim Jasmin Lapacz, Kathrin Ulrich, Jan Riemer","doi":"10.1111/febs.17328","DOIUrl":"https://doi.org/10.1111/febs.17328","url":null,"abstract":"<p><p>The mitochondrial disulphide relay machinery is essential for the import and oxidative folding of many proteins in the mitochondrial intermembrane space. Its core component, the import receptor MIA40 (also CHCHD4), serves as an oxidoreductase but also as a chaperone holdase, which initially interacts with its substrates non-covalently before introducing disulphide bonds for folding and retaining proteins in the intermembrane space. Interactome studies have identified diverse substrates of MIA40, among them the intrinsically disordered HCLS1-associated protein X-1 (HAX1). Interestingly, this protein does not contain cysteines, raising the question of how and to what end HAX1 can interact with MIA40. Here, we demonstrate that MIA40 non-covalently interacts with HAX1 independent of its redox-active cysteines. While HAX1 import is driven by its weak mitochondrial targeting sequence, its subsequent transient interaction with MIA40 stabilizes the protein in the intermembrane space. HAX1 solely depends on the holdase activity of MIA40, and the absence of MIA40 results in the aggregation, degradation and loss of HAX1. Collectively, our study introduces HAX1 as the first endogenous MIA40 substrate without cysteines and demonstrates the diverse functions of this highly conserved oxidoreductase and import receptor.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper inactivates DcsB by oxidizing the metal ligand Cys86 to sulfinic acid.","authors":"Kosuke Oda, Kenji Komaguchi, Yasuyuki Matoba","doi":"10.1111/febs.17325","DOIUrl":"https://doi.org/10.1111/febs.17325","url":null,"abstract":"<p><p>N^ω-hydroxy-l-arginine amidinohydrolase (EC:3.5.3.25), an enzyme in the d-cycloserine (d-CS) biosynthetic pathway of Streptomyces lavendulae, catalyzes the hydrolysis of an arginase inhibitor, N^ω-hydroxy-l-arginine, to produce l-ornithine and hydroxyurea, despite being homologous to arginase. Like arginase, the enzyme (DcsB) possesses two manganese ions (Mn_A and Mn_B) essential for the enzymatic reaction at the bottom of the cavity formed within the molecule. However, one of the Mn_A ligands in DcsB is Cys86, whereas the corresponding residues in arginase are histidine. In this study, we determined the crystal structure of Mn-free DcsB to elucidate the installation mechanism of the manganese ions. The flipping of the His111 residue after the formation of the coordination bond to the second manganese ion may facilitate the installation of Mn_B and the closing of the cavity entrance to retain Mn_A and Mn_B at the active site. Copper ions, which are known to be a positive regulator of many secondary metabolites in Streptomyces species, were found to irreversibly inactivate the catalytic activity of DcsB. Mass spectrometric and crystallographic analyses of the Cu(II)-treated DcsB indicated that Cys86 is oxidized to sulfinic acid. The d-CS biosynthesis in the producing microorganism may be negatively regulated by the concentration of intracellular copper ions, which mediates the oxidative stress.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in solid-state nuclear magnetic resonance studies on membrane fusion proteins.","authors":"Lifen Zheng, Shenlin Wang","doi":"10.1111/febs.17313","DOIUrl":"https://doi.org/10.1111/febs.17313","url":null,"abstract":"<p><p>Membrane fusion is an essential biological process that merges two separate lipid bilayers into a whole one. Membrane fusion proteins facilitate this process by bringing lipid bilayers in close proximity to reduce the repulsive energy between membranes. Along with their interactions with membranes, the structures and dynamics of membrane fusion proteins are key to elucidating the mechanisms of membrane fusion. Solid-state NMR (SSNMR) spectroscopy has unique advantages in determining the structures and dynamics of membrane fusion proteins in their membrane-bound states. It has been extensively applied to reveal conformational changes in intermediate states of viral membrane fusion proteins and to characterize the critical lipid-membrane interactions that drive the fusion process. In this review, we summarize recent advancements in SSNMR techniques for studying membrane fusion proteins and their applications in elucidating the mechanisms of membrane fusion.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The calcium-sensing receptor alleviates endothelial inflammation in atherosclerosis through regulation of integrin β1-NLRP3 inflammasome.","authors":"Yunge Jiang, Wenjing Xing, Zhong Li, Defeng Zhao, Bingxu Xiu, Yuhui Xi, Shuzhi Bai, Xiaoxue Li, Zheqi Zhang, Weihua Zhang, Hongxia Li","doi":"10.1111/febs.17308","DOIUrl":"https://doi.org/10.1111/febs.17308","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory disease of arteries. Endothelial inflammation is key to the initiation and development of AS. The calcium-sensing receptor (CaSR) is expressed in endothelial cells (ECs) but its role in endothelial inflammation during AS remains unclear. This study focused on the involvement of CaSR in regulating endothelial inflammation and its underlying mechanisms, providing novel insights for AS therapy. Here, we observed that CaSR agonist NPS-R568 significantly reduced atherosclerotic lesions and aortic inflammation in high-fat diet (HFD)-fed ApoE^-/- mice, while enhancing the expression of CaSR in aortic tissues. In vitro, human umbilical vein endothelial cells (HUVECs) exposed to oxidized low-density lipoprotein (oxLDL) at 20 μg·mL^-1 triggered inflammation, as indicated by the upregulation of vascular cell adhesion molecule-1 (VCAM-1), interleukin (IL)-6, and IL-1β expression, along with increased adherence of THP-1 or U937 cells to the HUVECs. Additionally, treatment with 20 μg·mL^-1 oxLDL led to downregulation of CaSR expression in HUVECs. The administration of CaSR agonist NPS-R568 or overexpression of CaSR in HUVECs resulted in a significant reversal of inflammation induced by oxLDL. Mechanistically, CaSR was found to mitigate NLRP3 inflammasome activation by downregulating the protein level of integrin β1. In conclusion, our study elucidates the beneficial role of CaSR in reducing endothelial inflammation in AS through the regulation of integrin β1 and the subsequent NLRP3 inflammasome. CaSR emerges as a promising target for potential therapeutic interventions in AS.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new player in the game: identification of C1ql1 as a novel factor driving OPC differentiation.","authors":"Jana Van Broeckhoven, Femke Mussen, Melissa Schepers, Tim Vanmierlo, Niels Hellings","doi":"10.1111/febs.17321","DOIUrl":"https://doi.org/10.1111/febs.17321","url":null,"abstract":"<p><p>Oligodendrocytes (OLGs) are the myelin-producing cells in the central nervous system (CNS). Following injury, these cells are prone to death, leading to demyelination and, eventually, axonal loss and neurodegeneration. Upon injury, the damaged CNS repopulates the lesion with oligodendrocyte precursor cells (OPCs) that consequently mature into OLGs to repair the myelin damage and prevent further axonal loss. In this issue, Altunay et al. identified that complement component 1, q subcomponent-like-1 (C1ql1), a factor known to play a role in neuron-neuron synapses, is also expressed by OPCs and drives their differentiation into OLGs. These data suggest that C1ql1 or other downstream factors could be therapeutic targets in the context of demyelinating disorders in which remyelination fails, such as in multiple sclerosis (MS).</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ionizing radiation inhibits zebrafish embryo hatching through induction of tissue inhibitors of metalloproteinases (TIMPs) expression.","authors":"Eun Jung Kwon, Hansong Lee, Unbum Shin, Eun-Sun Kim, Kyungjae Myung, Jeongmo Kim, Jung-Hoon Park, Kihun Kim, Yoonsung Lee, Chang-Kyu Oh, Yun Hak Kim","doi":"10.1111/febs.17318","DOIUrl":"https://doi.org/10.1111/febs.17318","url":null,"abstract":"<p><p>Ionizing radiation (IR) has garnered growing attention because of its biological effects on aquatic organisms and humans. Here, we identify the most impacted organs and uncover the molecular mechanisms causing the changes in the context of vertebrate development using single-cell RNA sequencing. Alterations in cellular composition and biological functions were explored using transcriptomic profiling of zebrafish embryos exposed to 5 Gy. Single-cell RNA sequencing analyses unveiled notable shifts in the proportions of brain/central nervous system and hatching gland clusters. Although IR exposure led to increased expression of hatching enzymes, a significant but mild delay in hatching was observed following 5 Gy IR exposure. Gene Ontology analysis showed an increased expression of tissue inhibitors of metalloproteinases (TIMPs), known as matrix metalloproteinase inhibitors, which was confirmed via whole-mount in situ hybridization. Correlation analysis linked TIMPs to transcription factors cebpb and cebpd, which were significantly correlated post-IR exposure. Although no morphological changes were observed in some organs, including the brain, the study reveals substantial alterations in developing vertebrates. Notably, despite increased hatching enzymes, elevated TIMPs in the hatching gland suggest a regulatory mechanism impacting hatching activity. This research contributes to comprehending the ecological repercussions of IR exposure, emphasizing the importance of safety measures for aquatic ecosystems and overall environmental health.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria: great balls of fire.","authors":"Howard T Jacobs, Pierre Rustin, Paule Bénit, Dan Davidi, Mügen Terzioglu","doi":"10.1111/febs.17316","DOIUrl":"https://doi.org/10.1111/febs.17316","url":null,"abstract":"<p><p>Recent experimental studies indicate that mitochondria in mammalian cells are maintained at temperatures of at least 50 °C. While acknowledging the limitations of current experimental methods and their interpretation, we here consider the ramifications of this finding for cellular functions and for evolution. We consider whether mitochondria as heat-producing organelles had a role in the origin of eukaryotes and in the emergence of homeotherms. The homeostatic responses of mitochondrial temperature to externally applied heat imply the existence of a molecular heat-sensing system in mitochondria. While current findings indicate high temperatures for the innermost compartments of mitochondria, those of the mitochondrial surface and of the immediately surrounding cytosol remain to be determined. We ask whether some aspects of mitochondrial dynamics and motility could reflect changes in the supply and demand for mitochondrial heat, and whether mitochondrial heat production could be a factor in diseases and immunity.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}