The FEBS journal最新文献_第10页

TRIM2: a double-edged sword preventing apoptosis TRIM2：防止细胞凋亡的双刃剑。

The FEBS journal Pub Date : 2024-12-01 DOI: 10.1111/febs.17342

Thomas Hollemann

引用次数: 0

Oxidative pathways of apo, partially, and fully Zn(II)- and Cd(II)-metalated human metallothionein-3 are dominated by disulfide bond formation 载子、部分和完全锌（II）和镉（II）金属化的人金属硫蛋白-3的氧化途径主要是二硫键形成。

The FEBS journal Pub Date : 2024-12-01 DOI: 10.1111/febs.17333

Amelia T. Yuan, Martin J. Stillman

{"title":"Oxidative pathways of apo, partially, and fully Zn(II)- and Cd(II)-metalated human metallothionein-3 are dominated by disulfide bond formation","authors":"Amelia T. Yuan, Martin J. Stillman","doi":"10.1111/febs.17333","DOIUrl":"10.1111/febs.17333","url":null,"abstract":"Oxidative stress is a key component of many diseases, including neurodegenerative diseases such as Alzheimer's disease. Reactive oxygen species (ROS) such as hydrogen peroxide and nitric oxide lead to disease progression by binding to proteins and causing their dysregulation. Metallothionein-3 (MT3), a cysteine-rich brain-located metalloprotein, has been proposed to be a key player in controlling oxidative stress in the central nervous system. We report data from a combination of electrospray ionization mass spectrometry (ESI-MS), ultraviolet (UV)-visible absorption spectroscopy, and circular dichroism spectroscopy that identify the oxidation pathway of MT3 fully bound to endogenous Zn(II) or exogenous Cd(II) together with the partially metalated species. We characterize the intermediate species formed during the oxidation of MT3, which is dominated by disulfide bond formation. We report the rates of oxidation. For both fully and partially metalated MT3, MT3 is oxidized at 5 to 10 times the rate of MT1, a similar but kidney-expressed isoform of MT. As oxidation progresses, MT3 follows a domain-specific demetallation pathway when it is fully metalated, and a domain-independent pathway when partially metalated. This suggests the presence of a significant susceptibility toward oxidation when MT3 is partially metalated, and, therefore, a possible protective role of Zn(II) when fully metalated. With the evidence for the rapid oxidation rate, our data support the proposals of MT3 as a key antioxidant in physiology.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 3","pages":"619-634"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.17333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 universal role of adaptive transcription in health and disease. 适应性转录在健康和疾病中的普遍作用。

The FEBS journal Pub Date : 2024-11-28 DOI: 10.1111/febs.17324

Thomas Lissek

{"title":"The universal role of adaptive transcription in health and disease.","authors":"Thomas Lissek","doi":"10.1111/febs.17324","DOIUrl":"https://doi.org/10.1111/febs.17324","url":null,"abstract":"In animals, adaptive transcription is a crucial mechanism to connect environmental stimulation to changes in gene expression and subsequent organism remodeling. Adaptive transcriptional programs involving molecules such as CREB, SRF, MEF2, FOS, and EGR1 are central to a wide variety of organism functions, including learning and memory, immune system plasticity, and muscle hypertrophy, and their activation increases cellular resilience and prevents various diseases. Yet, they also form the basis for many maladaptive processes and are involved in the progression of addiction, depression, cancer, cardiovascular disorders, autoimmune conditions, and metabolic dysfunction among others and are thus prime examples for mediating the adaptation-maladaptation dilemma. They are implicated in the therapeutic effects of major treatment modalities such as antidepressants and can have negative effects on treatment, for example, contributing to therapy resistance in cancer. This review examines the universal role of adaptive transcription as a mechanism for the induction of adaptive cell state transitions in health and disease and explores how many medical disorders can be conceptualized as caused by errors in cellular adaptation goals. It also considers the underlying principles in the basic structure of adaptive gene programs such as their division into a core and a directional program. Finally, it analyses how one might best reprogram cells via targeting of adaptive transcription in combination with complex stimulation patterns to leverage endogenous cellular reprogramming dynamics and achieve optimal health of the whole organism.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752810","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}

引用次数: 0

Transition metal transporting P-type ATPases: terminal metal-binding domains serve as sensors for autoinhibitory tails. 传递p型atp酶的过渡金属：末端金属结合域作为自抑制尾部的传感器。

The FEBS journal Pub Date : 2024-11-28 DOI: 10.1111/febs.17330

Qiaoxia Hu, Oleg Sitsel, Viktoria Bågenholm, Christina Grønberg, Pin Lyu, Anna Sigrid Pii Svane, Kasper Røjkjær Andersen, Nick Stub Laursen, Gabriele Meloni, Poul Nissen, Dennis W Juhl, Jakob Toudahl Nielsen, Niels Chr Nielsen, Pontus Gourdon

{"title":"Transition metal transporting P-type ATPases: terminal metal-binding domains serve as sensors for autoinhibitory tails.","authors":"Qiaoxia Hu, Oleg Sitsel, Viktoria Bågenholm, Christina Grønberg, Pin Lyu, Anna Sigrid Pii Svane, Kasper Røjkjær Andersen, Nick Stub Laursen, Gabriele Meloni, Poul Nissen, Dennis W Juhl, Jakob Toudahl Nielsen, Niels Chr Nielsen, Pontus Gourdon","doi":"10.1111/febs.17330","DOIUrl":"10.1111/febs.17330","url":null,"abstract":"Copper is an essential micronutrient and yet is highly toxic to cells at elevated concentrations. P1B-ATPase proteins are critical for this regulation, providing active extrusion across cellular membranes. One unique molecular adaptation of P1B-ATPases compared to other P-type ATPases is the presence of metal-binding domains (MBDs) at the cytosolic termini, which however are poorly characterized with an elusive mechanistic role. Here we present the MBD architecture in metal-free and metal-bound forms of the archetype Cu+-specific P1B-ATPase LpCopA, determined using NMR. The MBD is composed of a flexible tail and a structured core with a metal ion binding site defined by three sulfur atoms, one of which is pertinent to the so-called CXXC motif. Furthermore, we demonstrate that the MBD rather than being involved in ion delivery likely serves a regulatory role, which is dependent on the classical P-type ATPase E1-E2 transport mechanism. Specifically, the flexible tail appears responsible for autoinhibition while the metal-binding core is used for copper sensing. This model is validated by a conformation-sensitive and MBD-targeting nanobody that can structurally and functionally replace the flexible tail. We propose that autoinhibition of Cu+-ATPases occurs at low copper conditions via MBD-mediated interference with the soluble domains of the ATPase core and that metal transport is enabled when copper levels rise, through metal-induced dissociation of the MBD. This allows P1B-ATPase 'vacuum cleaners' to tune their own activity, balancing the levels of critical micronutrients in the cells.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752812","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}

引用次数: 0

Ruminococcus gnavus in the gut: driver, contributor, or innocent bystander in steatotic liver disease? 肠道中的反刍球菌：脂肪肝的驱动者、促成者还是无辜的旁观者？

The FEBS journal Pub Date : 2024-11-26 DOI: 10.1111/febs.17327

Vik Meadows, Jayson M Antonio, Ronaldo P Ferraris, Nan Gao

{"title":"Ruminococcus gnavus in the gut: driver, contributor, or innocent bystander in steatotic liver disease?","authors":"Vik Meadows, Jayson M Antonio, Ronaldo P Ferraris, Nan Gao","doi":"10.1111/febs.17327","DOIUrl":"10.1111/febs.17327","url":null,"abstract":"The human gut microbiome plays a crucial role in regulating intestinal and systemic health, impacting host immune response and metabolic function. Dysbiosis of the gut microbiome is linked to various diseases, including steatotic liver diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), a chronic liver disease characterized by excess hepatic lipid content and impaired metabolism, is the leading cause of liver disease worldwide. Among the gut microbes, Ruminococcus gnavus (R. gnavus) has garnered attention for its association with inflammatory and metabolic diseases. While R. gnavus abundance correlates to liver fat accumulation, further research is needed to identify a causal role or therapeutic intervention in steatotic liver disease. This review surveys our current understanding of R. gnavus in the development and progression of steatotic liver diseases, highlighting its potential mechanisms through metabolite secretion, and emphasizes the need for comprehensive microbiome analyses and longitudinal studies to better understand R. gnavus' impact on liver health. This knowledge could pave the way for targeted interventions aimed at modulating gut microbiota to treat and prevent MASLD and its comorbidities.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":"e17327"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735485","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}

引用次数: 0

AXIN2 is a non-redundant regulator of AXIN1 stability and β-catenin in colorectal cancer cells. AXIN2 是结直肠癌细胞中 AXIN1 稳定性和β-catenin 的非冗余调节因子。

The FEBS journal Pub Date : 2024-11-25 DOI: 10.1111/febs.17336

Lin Liu, John Silke

引用次数: 0

Antioxidant properties of the soluble carotenoprotein AstaP and its feasibility for retinal protection against oxidative stress 可溶性胡萝卜素蛋白 AstaP 的抗氧化特性及其保护视网膜免受氧化应激的可行性。

The FEBS journal Pub Date : 2024-11-24 DOI: 10.1111/febs.17335

Daria A. Lunegova, Danil A. Gvozdev, Ivan I. Senin, Victoria R. Gudkova, Svetlana V. Sidorenko, Veronika V. Tiulina, Natalia G. Shebardina, Marina A. Yakovleva, Tatiana B. Feldman, Alla A. Ramonova, Anastasia M. Moysenovich, Alexey N. Semenov, Evgeni Yu. Zernii, Eugene G. Maksimov, Nikolai N. Sluchanko, Mikhail P. Kirpichnikov, Mikhail A. Ostrovsky

{"title":"Antioxidant properties of the soluble carotenoprotein AstaP and its feasibility for retinal protection against oxidative stress","authors":"Daria A. Lunegova, Danil A. Gvozdev, Ivan I. Senin, Victoria R. Gudkova, Svetlana V. Sidorenko, Veronika V. Tiulina, Natalia G. Shebardina, Marina A. Yakovleva, Tatiana B. Feldman, Alla A. Ramonova, Anastasia M. Moysenovich, Alexey N. Semenov, Evgeni Yu. Zernii, Eugene G. Maksimov, Nikolai N. Sluchanko, Mikhail P. Kirpichnikov, Mikhail A. Ostrovsky","doi":"10.1111/febs.17335","DOIUrl":"10.1111/febs.17335","url":null,"abstract":"Photodamage to the outer segments of photoreceptor cells and their impaired utilization by retinal pigment epithelium (RPE) cells contribute to the development of age-related macular degeneration (AMD) leading to blindness. Degeneration of photoreceptor cells and RPE cells is triggered by reactive oxygen species (ROS) produced by photochemical reactions involving bisretinoids, by-products of the visual cycle, which accumulate in photoreceptor discs and lipofuscin granules of RPE. Carotenoids, natural antioxidants with high potential efficacy against a wide range of ROS, may protect against the cytotoxic properties of lipofuscin. To solve the problem of high hydrophobicity of carotenoids and increase their bioaccessibility, specialized proteins can ensure their targeted delivery to the affected tissues. In this study, we present new capabilities of the recombinant water-soluble protein AstaP from Coelastrella astaxanthina Ki-4 (Scenedesmaceae) for protein-mediated carotenoid delivery and demonstrate how zeaxanthin delivery suppresses oxidative stress in a lipofuscin-enriched model of photoreceptor and pigment epithelium cells. AstaP in complex with zeaxanthin can effectively scavenge various ROS (singlet oxygen, free radical cations, hydrogen peroxide) previously reported to be generated in AMD. In addition, we explore the potential of optimizing the structure of AstaP to enhance its thermal stability and resistance to proteolytic activity in the ocular media. This optimization aims to maximize the prevention of retinal degenerative changes in AMD.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 2","pages":"355-372"},"PeriodicalIF":0.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712330","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}

引用次数: 0

Regulation of the HMGA2-SNAI2/CXCR4 axis in atherosclerosis and retinal neovascularization: new therapeutic insights 动脉粥样硬化和视网膜新生血管中 HMGA2-SNAI2/CXCR4 轴的调控：治疗新见解。

The FEBS journal Pub Date : 2024-11-22 DOI: 10.1111/febs.17300

Jianan Li, Zhuxi Liu, Chunyong Yu, Weilong Song, Xiaobin Zhang, Guobiao Liang

{"title":"Regulation of the HMGA2-SNAI2/CXCR4 axis in atherosclerosis and retinal neovascularization: new therapeutic insights","authors":"Jianan Li, Zhuxi Liu, Chunyong Yu, Weilong Song, Xiaobin Zhang, Guobiao Liang","doi":"10.1111/febs.17300","DOIUrl":"10.1111/febs.17300","url":null,"abstract":"Atherosclerosis (AS) is a vascular disease associated with endothelial damage, plaque formation, and retinal neovascularization (RNV), leading to visual impairment. Research indicates that vascular endothelial dysfunction, lipid deposition, and inflammatory responses contribute to the formation of plaques and atherosclerotic lesions. Among the common complications, studies have shown that RNV and the molecular mechanisms of AS hold significant clinical importance. In this study, we identified the overexpression of the gene heat shock protein 90 (HSP90) through transcriptome sequencing. Subsequent protein expression analysis and inhibition experiments in corresponding animal models confirmed the crucial role of HSP90 in the modulation of this disease. Research findings revealed an increase in the expression of HSP90, HMGA2, Snail family transcriptional repressor 2 gene (SNAI2), CXC chemokine receptor 4 (CXCR4), and vascular endothelial growth factor (VEGF) in atherosclerotic mouse tissues. Inhibition of HSP90 expression reduced vascular neovascularization and downregulated the expression of HMGA2 and VEGF. Given that HSP90 can promote HMGA2 expression, which, in turn, facilitates angiogenesis, we conducted lentiviral infection experiments on primary retinal endothelial cells obtained from atherosclerotic mice, confirming the regulatory role of HSP90 in modulating HMGA2 expression through the SNAI2/CXCR4 signaling pathway and its involvement in retinal endothelial neovascularization. In conclusion, our study highlights the significant regulatory role of HSP90 in AS-induced RNV, providing a new target for disease treatment. Furthermore, this research extensively explores the mechanism of HSP90 in regulating RNV and associated signaling pathways, offering novel insights and laying a solid foundation for future studies in this disease domain.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 1","pages":"168-190"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694072","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}

引用次数: 0

Paradigms of convergent evolution in enzymes 酶的趋同进化范例。

The FEBS journal Pub Date : 2024-11-22 DOI: 10.1111/febs.17332

Ioannis G. Riziotis, Jenny C. Kafas, Gabriel Ong, Neera Borkakoti, António J. M. Ribeiro, Janet M. Thornton

{"title":"Paradigms of convergent evolution in enzymes","authors":"Ioannis G. Riziotis, Jenny C. Kafas, Gabriel Ong, Neera Borkakoti, António J. M. Ribeiro, Janet M. Thornton","doi":"10.1111/febs.17332","DOIUrl":"10.1111/febs.17332","url":null,"abstract":"There are many occurrences of enzymes catalysing the same reaction but having significantly different structures. Leveraging the comprehensive information on enzymes stored in the Mechanism and Catalytic Site Atlas (M-CSA), we present a collection of 34 cases for which there is sufficient evidence of functional convergence without an evolutionary link. For each case, we compare enzymes which have identical Enzyme Commission numbers (i.e. catalyse the same reaction), but different identifiers in the CATH data resource (i.e. different folds). We focus on similarities between their sequences, structures, active site geometries, cofactors and catalytic mechanisms. These features are then assessed to evaluate whether all the evidence for these structurally diverse proteins supports their independent evolution to catalyse the same chemical reaction. Our approach combines published literature information with knowledge-based computational resources from, amongst others, M-CSA, PDBe and PDBsum, supported by tailor-made software to explore active site structures and assess similarities in mechanism. We find that there are multiple types of convergent functional evolution observed to date, and it is necessary to investigate sequence, structure, active site geometry and enzyme mechanisms to describe such convergence accurately.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 3","pages":"537-555"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.17332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protection of beta cells against cytokine-induced apoptosis by the gut microbial metabolite butyrate 肠道微生物代谢物丁酸盐保护β细胞免受细胞因子诱导的凋亡。

The FEBS journal Pub Date : 2024-11-21 DOI: 10.1111/febs.17334

Kasper Suhr Jørgensen, Signe Schultz Pedersen, Siv Annegrethe Hjorth, Nils Billestrup, Michala Prause

{"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":"10.1111/febs.17334","url":null,"abstract":"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.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 1","pages":"226-240"},"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}

引用次数: 0