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Metabolic dysregulation-triggered neutrophil extracellular traps exacerbate acute liver failure 代谢失调触发的中性粒细胞胞外捕获物会加剧急性肝衰竭。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-18 DOI: 10.1002/1873-3468.14971
Kangnan Zhang, Rongrong Jia, Qinghui Zhang, Shihao Xiang, Na Wang, Ling Xu
{"title":"Metabolic dysregulation-triggered neutrophil extracellular traps exacerbate acute liver failure","authors":"Kangnan Zhang,&nbsp;Rongrong Jia,&nbsp;Qinghui Zhang,&nbsp;Shihao Xiang,&nbsp;Na Wang,&nbsp;Ling Xu","doi":"10.1002/1873-3468.14971","DOIUrl":"10.1002/1873-3468.14971","url":null,"abstract":"<p>Acute liver failure (ALF) is an acute liver disease with a high mortality rate in clinical practice, characterized histologically by extensive hepatocellular necrosis and massive neutrophil infiltration. However, the role of these abnormally infiltrating neutrophils during ALF development is unclear. Here, in an ALF mouse model, metabolites were identified that promote the formation of neutrophil extracellular traps (NETs) in the liver, subsequently influencing macrophage differentiation and disease progression. ALF occurs with abnormalities in hepatic and intestinal metabolites. Abnormal metabolites (LTD4 and glutathione) can directly, or indirectly <i>via</i> reactive oxygen species, promote NET formation of infiltrating neutrophils, which subsequently regulate macrophages in a pro-inflammatory M1-like state, inducing an amplification of the destructive effects of inflammation. Together, this study provides new insights into the role of NETs in the pathogenesis of ALF.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 miR-26a/SIRT6/HIF-1α axis regulates glycolysis and inflammatory responses in host macrophages during Mycobacterium tuberculosis infection 在结核分枝杆菌感染期间，miR-26a/SIRT6/HIF-1α轴调节宿主巨噬细胞中的糖酵解和炎症反应。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-18 DOI: 10.1002/1873-3468.15001
Soumya Mal, Debayan Majumder, Pankaj Birari, Arun Kumar Sharma, Umesh Gupta, Kuladip Jana, Manikuntala Kundu, Joyoti Basu
{"title":"The miR-26a/SIRT6/HIF-1α axis regulates glycolysis and inflammatory responses in host macrophages during Mycobacterium tuberculosis infection","authors":"Soumya Mal,&nbsp;Debayan Majumder,&nbsp;Pankaj Birari,&nbsp;Arun Kumar Sharma,&nbsp;Umesh Gupta,&nbsp;Kuladip Jana,&nbsp;Manikuntala Kundu,&nbsp;Joyoti Basu","doi":"10.1002/1873-3468.15001","DOIUrl":"10.1002/1873-3468.15001","url":null,"abstract":"<p><i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is the causative agent of tuberculosis. Here, a macrophage infection model was used to unravel the role of the histone deacetylase sirtuin 6 (SIRT6) in <i>Mtb</i>-triggered regulation of the innate immune response. <i>Mtb</i> infection downregulated microRNA-26a and upregulated its target SIRT6. SIRT6 suppressed glycolysis and expression of HIF-1α-dependent glycolytic genes during infection. In addition, SIRT6 regulated the levels of intracellular succinate which controls stabilization of HIF-1α, as well as the release of interleukin (IL)-1β. Furthermore, SIRT6 inhibited inducible nitric oxide synthase (iNOS) and proinflammatory IL-6 but augmented anti-inflammatory arginase expression. The miR-26a/SIRT6/HIF-1α axis therefore regulates glycolysis and macrophage immune responses during <i>Mtb</i> infection. Our findings link SIRT6 to rewiring of macrophage signaling pathways facilitating dampening of the antibacterial immune response.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 role of Lin28A and Lin28B in cancer beyond Let-7. Lin28A和Lin28B在癌症中的作用超越了Let-7。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-16 DOI: 10.1002/1873-3468.15004
Sandra Cotino-Nájera, Enrique García-Villa, Samantha Cruz-Rosales, Patricio Gariglio, José Díaz-Chávez
{"title":"The role of Lin28A and Lin28B in cancer beyond Let-7.","authors":"Sandra Cotino-Nájera, Enrique García-Villa, Samantha Cruz-Rosales, Patricio Gariglio, José Díaz-Chávez","doi":"10.1002/1873-3468.15004","DOIUrl":"https://doi.org/10.1002/1873-3468.15004","url":null,"abstract":"<p><p>Lin28A and Lin28B are paralogous RNA-binding proteins that play fundamental roles in development and cancer by regulating the microRNA family of tumor suppressor Let-7. Although Lin28A and Lin28B share some functional similarities with Let-7 inhibitors, they also have distinct expression patterns and biological functions. Increasing evidence indicates that Lin28A and Lin28B differentially impact cancer stem cell properties, epithelial-mesenchymal transition, metabolic reprogramming, and other hallmarks of cancer. Therefore, it is important to understand the overexpression of Lin28A and Lin28B paralogs in specific cancer contexts. In this review, we summarize the main similarities and differences between Lin28A and Lin28B, their implications in different cellular processes, and their role in different types of cancer. In addition, we provide evidence of other specific targets of each lin28 paralog, as well as the lncRNAs and miRNAs that promote or inhibit its expression, and how this impacts cancer development and progression.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 unfolded protein response sensor PERK mediates mechanical stress-induced maturation of focal adhesion complexes in glioblastoma cells. 未折叠蛋白反应传感器PERK介导了机械应力诱导的胶质母细胞瘤细胞局灶粘附复合物的成熟。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-16 DOI: 10.1002/1873-3468.14996
Mohammad Khoonkari, Dong Liang, Marleen Kamperman, Patrick van Rijn, Frank A E Kruyt
{"title":"The unfolded protein response sensor PERK mediates mechanical stress-induced maturation of focal adhesion complexes in glioblastoma cells.","authors":"Mohammad Khoonkari, Dong Liang, Marleen Kamperman, Patrick van Rijn, Frank A E Kruyt","doi":"10.1002/1873-3468.14996","DOIUrl":"https://doi.org/10.1002/1873-3468.14996","url":null,"abstract":"<p><p>Stiffening of the brain extracellular matrix (ECM) in glioblastoma promotes tumor progression. Previously, we discovered that protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) plays a role in glioblastoma stem cell (GSC) adaptation to matrix stiffness through PERK/FLNA-dependent F-actin remodeling. Here, we examined the involvement of PERK in detecting stiffness changes via focal adhesion complex (FAC) formation. Compared to control GSCs, PERK-deficient GSCs show decreased vinculin and tensin expression, while talin and integrin-β1 remain constant. Furthermore, vimentin was also reduced while tubulin increased, and a stiffness-dependent increase of the differentiation marker GFAP expression was absent in PERK-deficient GSCs. In conclusion, our study reveals a novel role for PERK in FAC formation during matrix stiffening, which is likely linked to its regulation of F-actin remodeling.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 and enzyme engineering of the broad substrate spectrum l-amino acid oxidase 4 from the fungus Hebeloma cylindrosporum 来自真菌圆柱孢 Hebeloma cylindrosporum 的广底物谱 l- 氨基酸氧化酶 4 的晶体结构和酶工程。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-16 DOI: 10.1002/1873-3468.15002
Simon Koopmeiners, Dominic Gilzer, Christiane Widmann, Nils Berelsmann, Jens Sproß, Hartmut H. Niemann, Gabriele Fischer von Mollard
{"title":"Crystal structure and enzyme engineering of the broad substrate spectrum l-amino acid oxidase 4 from the fungus Hebeloma cylindrosporum","authors":"Simon Koopmeiners,&nbsp;Dominic Gilzer,&nbsp;Christiane Widmann,&nbsp;Nils Berelsmann,&nbsp;Jens Sproß,&nbsp;Hartmut H. Niemann,&nbsp;Gabriele Fischer von Mollard","doi":"10.1002/1873-3468.15002","DOIUrl":"10.1002/1873-3468.15002","url":null,"abstract":"<p><span>l</span>-Amino acid oxidases (LAAOs) catalyze the oxidative deamination of <span>l</span>-amino acids to α-keto acids. Recombinant production of LAAOs with broad substrate spectrum remains a formidable challenge. We previously achieved this for the highly active and thermostable LAAO4 of <i>Hebeloma cylindrosporum</i> (<i>Hc</i>LAAO4). Here, we crystallized a proteolytically truncated surface entropy reduction variant of <i>Hc</i>LAAO4 and solved its structure in substrate-free form and in complex with diverse substrates. The ability to support the aliphatic portion of a substrate's side chain by an overall hydrophobic active site is responsible for the broad substrate spectrum of <i>Hc</i>LAAO4, including <span>l</span>-amino acids with big aromatic, acidic and basic side chains. Based on the structural findings, we generated an E288H variant with increased activity toward pharmaceutical building blocks of high interest.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
T-cell immunosuppression in sepsis is augmented by sciatic denervation-induced skeletal muscle atrophy 坐骨神经支配引起的骨骼肌萎缩增强了败血症中的 T 细胞免疫抑制。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-08 DOI: 10.1002/1873-3468.14999
Sumika Osa, Yuki Enoki, Daisuke Takahashi, Victor Tuan Giam Chuang, Kazuaki Taguchi, Kazuaki Matsumoto
{"title":"T-cell immunosuppression in sepsis is augmented by sciatic denervation-induced skeletal muscle atrophy","authors":"Sumika Osa,&nbsp;Yuki Enoki,&nbsp;Daisuke Takahashi,&nbsp;Victor Tuan Giam Chuang,&nbsp;Kazuaki Taguchi,&nbsp;Kazuaki Matsumoto","doi":"10.1002/1873-3468.14999","DOIUrl":"10.1002/1873-3468.14999","url":null,"abstract":"<p>Skeletal muscle atrophy is a known risk factor for immunosuppressive conditions and for a poor prognosis in sepsis. However, its immunopathology has not been experimentally elucidated. This study investigated the effects of skeletal muscle atrophy on the immunopathology of sepsis. Male C57BL/6J mice were subjected to sciatic denervation (DN) and caecal ligation and puncture (CLP) to induce muscle atrophy or sepsis. The macrophages, myeloid-derived suppressor cells (MDSC), and T-cells in peritoneal and spleen were analysed using flow cytometry. DN-induced muscle atrophy did not affect macrophage and MDSC populations. In contrast, the percentage of cytotoxic T-lymphocyte-associated antigen (CTLA)-4<sup>+</sup> CD4<sup>+</sup> T-cells, programmed death (PD)-1<sup>+</sup> CD8<sup>+</sup> T-cells, regulatory T-cells, and the CTLA-4<sup>+</sup> regulatory T-cells was statistically significantly higher in DN-CLP mice than in sham-CLP mice. Skeletal muscle atrophy before sepsis triggers excessive T cell immunosuppression, which may contribute to the exacerbation of sepsis under skeletal muscle atrophy.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.14999","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
The hAtg8 protein GABARAP interacts with EGFR and supports its unique role during receptor trafficking hAtg8 蛋白 GABARAP 与表皮生长因子受体相互作用，支持其在受体迁移过程中发挥独特作用
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-08 DOI: 10.1002/1873-3468.14997
Alina Üffing, Oliver H. Weiergräber, Melanie Schwarten, Silke Hoffmann, Dieter Willbold
{"title":"The hAtg8 protein GABARAP interacts with EGFR and supports its unique role during receptor trafficking","authors":"Alina Üffing, Oliver H. Weiergräber, Melanie Schwarten, Silke Hoffmann, Dieter Willbold","doi":"10.1002/1873-3468.14997","DOIUrl":"https://doi.org/10.1002/1873-3468.14997","url":null,"abstract":"The human Atg8 family member GABARAP is involved in numerous autophagy‐related and ‐unrelated processes. We recently observed that specifically the deficiency of GABARAP enhances epidermal growth factor receptor (EGFR) degradation upon ligand stimulation. Here, we report on two putative LC3‐interacting regions (LIRs) within EGFR, the first of which (LIR1) is selected as a GABARAP binding site <jats:italic>in silico</jats:italic>. Indeed, <jats:italic>in vitro</jats:italic> interaction studies reveal preferential binding of LIR1 to GABARAP and GABARAPL1. Our X‐ray data demonstrate interaction of core LIR1 residues FLPV with both hydrophobic pockets of GABARAP suggesting canonical binding. Although LIR1 occupies the LIR docking site, GABARAP Y49 and L50 appear dispensable in this case. Our data support the hypothesis that GABARAP affects the fate of EGFR at least in part through direct binding.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141946008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 dual nature of TDC - bridging dendritic and T cells in immunity. 树突状细胞的双重性质--免疫中树突状细胞和 T 细胞的桥梁。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-08 DOI: 10.1002/1873-3468.14998
Maria Nelli, Mirela Kuka
{"title":"The dual nature of T<sub>DC</sub> - bridging dendritic and T cells in immunity.","authors":"Maria Nelli, Mirela Kuka","doi":"10.1002/1873-3468.14998","DOIUrl":"https://doi.org/10.1002/1873-3468.14998","url":null,"abstract":"<p><p>T<sub>DC</sub> are hematopoietic cells with unique features that provide intriguing insights into the interplay between innate and adaptive immunity. They express a combination of conventional dendritic cell (DC) and T-cell markers and are found in secondary lymphoid organs (SLOs), lungs and liver of naïve mice, as well as in human blood. When analyzed ex vivo, T<sub>DC</sub> can behave either as DCs or as T cells, depending on the provided stimuli. Notably, T<sub>DC</sub> numbers and activation significantly increase in SLOs following viral infection, suggesting a potential role for T<sub>DC</sub> in antiviral immune responses. In this review, we discuss the properties of these fascinating cells, which call for more investigation on their physiological role during immune responses to both pathogens and tumors.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Nrf2 as a regulator of energy metabolism and mitochondrial function Nrf2 是能量代谢和线粒体功能的调节器。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-08 DOI: 10.1002/1873-3468.14993
Alina Luchkova, Ana Mata, Susana Cadenas
{"title":"Nrf2 as a regulator of energy metabolism and mitochondrial function","authors":"Alina Luchkova,&nbsp;Ana Mata,&nbsp;Susana Cadenas","doi":"10.1002/1873-3468.14993","DOIUrl":"10.1002/1873-3468.14993","url":null,"abstract":"<p>Nuclear factor erythroid-2-related factor 2 (Nrf2) is essential for the control of cellular redox homeostasis. When activated, Nrf2 elicits cytoprotective effects through the expression of several genes encoding antioxidant and detoxifying enzymes. Nrf2 can also improve antioxidant defense via the pentose phosphate pathway by increasing NADPH availability to regenerate glutathione. Microarray and genome-wide localization analyses have identified many Nrf2 target genes beyond those linked to its redox-regulatory capacity. Nrf2 regulates several intermediary metabolic pathways and is involved in cancer cell metabolic reprogramming, contributing to malignant phenotypes. Nrf2 also modulates substrate utilization for mitochondrial respiration. Here we review the experimental evidence supporting the essential role of Nrf2 in the regulation of energy metabolism and mitochondrial function.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.14993","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Oxidative stress and aging: synergies for age related diseases 氧化应激与衰老：与年龄相关疾病的协同作用。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-08-07 DOI: 10.1002/1873-3468.14995
Daniela F. Santos, Sónia Simão, Clévio Nóbrega, José Bragança, Pedro Castelo-Branco, Inês M. Araújo, ALFA Score Consortium
{"title":"Oxidative stress and aging: synergies for age related diseases","authors":"Daniela F. Santos,&nbsp;Sónia Simão,&nbsp;Clévio Nóbrega,&nbsp;José Bragança,&nbsp;Pedro Castelo-Branco,&nbsp;Inês M. Araújo,&nbsp;ALFA Score Consortium","doi":"10.1002/1873-3468.14995","DOIUrl":"10.1002/1873-3468.14995","url":null,"abstract":"<p>Aging is characterized by a progressive decline in physiological function and underlies several disabilities, including the increased sensitivity of cells and tissues to undergo pathological oxidative stress. In recent years, efforts have been made to better understand the relationship between age and oxidative stress and further develop therapeutic strategies to minimize the impact of both events on age-related diseases. In this work, we review the impact of the oxidant and antioxidant systems during aging and disease development and discuss the crosstalk of oxidative stress and other aging processes, with a focus on studies conducted in elderly populations.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.14995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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