Frontiers in cell death最新文献_第2页

Small heat shock proteins as modulators of cell death in Plasmodium falciparum parasites and its human host 作为恶性疟原虫及其人类宿主细胞死亡调节剂的小热休克蛋白

Frontiers in cell death Pub Date : 2023-11-29 DOI: 10.3389/fceld.2023.1322780

Francisca Magum Timothy, T. Zininga

{"title":"Small heat shock proteins as modulators of cell death in Plasmodium falciparum parasites and its human host","authors":"Francisca Magum Timothy, T. Zininga","doi":"10.3389/fceld.2023.1322780","DOIUrl":"https://doi.org/10.3389/fceld.2023.1322780","url":null,"abstract":"Plasmodium falciparum, the predominant cause of severe malaria, thrives within both poikilotherm mosquitoes and homeotherm humans, navigating challenging temperature shifts during its life cycle. Survival in such varying environments necessitate the development of robust mechanisms, including a sophisticated protein folding system to mitigate proteopathy. The parasite needs to control the survival of its host cells which affects its chances of development and propagation. Central to this system are heat shock proteins (Hsps), among which small Hsps (sHsps) play pivotal roles in maintaining proteostasis (protein homeostasis). In both humans and P. falciparum, numerous sHsps have been identified, making them attractive candidates as biomarkers for diagnostic and drug development strategies. Evidence is accumulating suggesting that these sHsps participate in cell death processes, potentially influencing disease pathogenesis. Despite their significance, the precise functions of sHsps in P. falciparum’s adaptation to stress conditions remains largely unknown. Comparative structural analysis of sHsps between human and P. falciparum reveals species-specific variations. Despite conserved tertiary structures, unique motifs are found in parasite sHsps which may modulate specialised chaperone functions. This review discusses the conserved and distinctive motifs of sHsps from the human host and the parasite, offering insights into shared and unique attributes. These findings illuminate the potential for species-specific targeting of sHsps, as players in cell death processes that may foster innovative biomarker identification approaches. As malaria continues to ravage Sub-Saharan Africa, understanding the molecular intricacies guiding parasite survival are essential in the development of interventions with heightened efficacy against this global health crisis.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139209681","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

Development of a cell-based model system for the investigation of ferroptosis 基于细胞的铁下垂研究模型系统的建立

Frontiers in cell death Pub Date : 2023-11-14 DOI: 10.3389/fceld.2023.1182239

Bjarne Goebel, Laura Carpanedo, Susanne Reif, Tamara Göbel, Svenja Simonyi, Nils Helge Schebb, Dieter Steinhilber, Ann-Kathrin Häfner

{"title":"Development of a cell-based model system for the investigation of ferroptosis","authors":"Bjarne Goebel, Laura Carpanedo, Susanne Reif, Tamara Göbel, Svenja Simonyi, Nils Helge Schebb, Dieter Steinhilber, Ann-Kathrin Häfner","doi":"10.3389/fceld.2023.1182239","DOIUrl":"https://doi.org/10.3389/fceld.2023.1182239","url":null,"abstract":"Since 2005, the original three cell death mechanisms apoptosis, autophagy and necrosis are accompanied by several new forms. The most recent member, ferroptosis, was first described in 2012 and is characterized by the accumulation of iron and increased lipid peroxidation. In this study, we present a model system to study ferroptotic states in stably transfected HEK293T cells, using acyl-CoA synthetase long chain family member 4 (ACSL4), a biomarker of ferroptosis, and/or lysophosphatidylcholine acyltransferase 2 (LPCAT2), a transferase responsible for the lipid remodeling process. In addition, we introduced an inducible expression system for 5-lipoxygenase (LO), 15-LO1 and 15-LO2, to trigger enzymatic lipid peroxidation. We characterized the system in terms of ACSL4, LPCAT2 and LO expression both on Western blot level and by laser scanning confocal microscopy as well as the intracellular localization of all enzymes. Furthermore, we verified inducibility and activity of our LOs and, in addition, analyzed non-esterified (free) and total amounts of oxylipins. When cells were incubated with the ferroptosis-inducing agents GPX4 inhibitor RSL3 or GSH reducing erastin, we observed a decrease in cell viability that was strongly enhanced in the presence of ACSL4 and LPCAT2. Interestingly, additional expression of LPCAT2 resulted in altered localization of 15-LO1, which shifted from the cytosol to the nuclear membrane. A similar localization occurred after treatment with RSL3. Therefore, on one hand, we propose that LPCAT2 is an acyltransferase that promotes ferroptotic conditions, and on the other hand, we introduce a new cell-based model system suitable for studying ferroptosis.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"46 27","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134901714","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

Molecular and temporal control of restimulation-induced cell death (RICD) in T lymphocytes T淋巴细胞再刺激诱导细胞死亡(RICD)的分子和时间控制

Frontiers in cell death Pub Date : 2023-10-30 DOI: 10.3389/fceld.2023.1281137

Katherine P. Lee, Benjamin Epstein, Camille M. Lake, Andrew L. Snow

{"title":"Molecular and temporal control of restimulation-induced cell death (RICD) in T lymphocytes","authors":"Katherine P. Lee, Benjamin Epstein, Camille M. Lake, Andrew L. Snow","doi":"10.3389/fceld.2023.1281137","DOIUrl":"https://doi.org/10.3389/fceld.2023.1281137","url":null,"abstract":"For effective adaptive immunity, T lymphocytes must rapidly expand and contract in an antigen-specific manner to effectively control invading pathogens and preserve immunological memory, without sustaining excessive collateral damage to host tissues. Starting from initial antigen encounter, carefully calibrated programmed cell death pathways are critical for maintaining homeostasis over distinct phases of the T cell response. Restimulation-induced cell death (RICD), a self-regulatory apoptosis pathway triggered by re-engagement of the T cell receptor (TCR), is particularly important for constraining effector T cell expansion to preclude overt immunopathology; indeed, genetic disorders affecting key molecules involved in RICD execution can manifest in excessive lymphoproliferation, malignancy, and autoimmunity. Herein we review our current knowledge of how RICD sensitivity is ultimately regulated over the course of an immune response, including recent revelations on molecules that tune RICD by enforcing resistance or promoting susceptibility in expanding versus mature effector T cells, respectively. Detailed dissection of the molecular and temporal control of RICD also illuminates novel therapeutic strategies for correcting abnormal T cell responses noted in various immune disorders by ultimately tuning RICD sensitivity.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"21 16","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136102801","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

Resistance to CLnA-induced ferroptosis is acquired in Caco-2 cells upon differentiation Caco-2细胞在分化过程中获得了对clna诱导的铁下垂的抗性

Frontiers in cell death Pub Date : 2023-08-29 DOI: 10.3389/fceld.2023.1219672

Géraldine Cuvelier, Perrine Vermonden, J. Rousseau, O. Féron, R. Rezsohazy, Y. Larondelle

{"title":"Resistance to CLnA-induced ferroptosis is acquired in Caco-2 cells upon differentiation","authors":"Géraldine Cuvelier, Perrine Vermonden, J. Rousseau, O. Féron, R. Rezsohazy, Y. Larondelle","doi":"10.3389/fceld.2023.1219672","DOIUrl":"https://doi.org/10.3389/fceld.2023.1219672","url":null,"abstract":"In contrast to canonical ferroptosis inducers, highly peroxidable conjugated linolenic acids (CLnA) directly fuel the lipid peroxidation cascade upon their incorporation into membrane phospholipids. Little is known, however, about the cytotoxicity level of CLnAs to normal epithelial cells. Caco-2 cells, derived from colorectal adenocarcinoma, spontaneously differentiate into enterocyte-like cells over a period of 21 days of cell culturing, allowing for graduated phenotypic shift from proliferative, undifferentiated cells to a functional intestinal barrier. We exploited this property to assess the sensitivity of Caco-2 cells to CLnAs at different stages of differentiation. Our results show a significant decrease in CLnA-induced ferroptotic cell death over time. The acquired resistance aligned with decreases in cell proliferation and in the extent of lipid peroxidation, as well as with an increase in the expression of GPX4 upon differentiation. These results highlight that while CLnAs are highly toxic for proliferating cancer cells, differentiated epithelial cells are resistant to CLnA-induced ferroptosis. Therefore, this study gives credential to the therapeutic use of CLnAs as an anticancer strategy and offers a new model study to further investigate the safety of peroxidable fatty acids in differentiated cells.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91081004","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

Dissecting the mechanism of regulation of a ferroptosis-like form of cell death in Drosophila melanogaster 解剖黑腹果蝇细胞凋亡样形式的调控机制

Frontiers in cell death Pub Date : 2023-06-20 DOI: 10.3389/fceld.2023.1209641

Sanjay Saini, Edward Owusu-Ansah

{"title":"Dissecting the mechanism of regulation of a ferroptosis-like form of cell death in Drosophila melanogaster","authors":"Sanjay Saini, Edward Owusu-Ansah","doi":"10.3389/fceld.2023.1209641","DOIUrl":"https://doi.org/10.3389/fceld.2023.1209641","url":null,"abstract":"Ferroptosis is a specific form of non-apoptotic cell death that is driven by iron-dependent phospholipid peroxidation. Research over the past decade has contributed to our understanding of how this important cell death process is regulated in mammalian systems, especially with regard to the distinct modes of induction, the role of metabolic signals, the organelles involved, implications of ferroptosis for development and aging, and how our improved understanding of the process can be exploited for therapeutic purposes. Other studies have described variants of this ancient cell death process in cyanobacteria, plants and protozoans. Emerging evidence indicates that a ferroptosis-like form of cell death exists in fruit flies (Drosophila melanogaster). Due to the extensive homology of genes in Drosophila melanogaster and Drosophila suzukii, unique aspects of ferroptosis in Drosophila melanogaster may be of particular relevance for developing targeted pesticides against Drosophila suzukii—a major invasive agricultural pest of the berry and wine industry in Southeast Asia, Europe and America. Further, aspects of ferroptosis in Drosophila melanogaster that are conserved in insects in general may provide the basis for identifying new insecticides for controlling the spread of vector-borne diseases such as malaria. In this perspective, we highlight some of the studies in Drosophila melanogaster that have sought to improve our understanding of the ferroptosis-like form of cell death that operates in this organism and conclude with a discussion of the opportunities and challenges for studying this phenomenon in fruit flies.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76954015","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

One-half century (or more) of study of cell death: origins, present, and perhaps future 半个世纪(或更久)的细胞死亡研究:起源，现在，也许还有未来

Frontiers in cell death Pub Date : 2023-06-16 DOI: 10.3389/fceld.2023.1197400

R. Lockshin

{"title":"One-half century (or more) of study of cell death: origins, present, and perhaps future","authors":"R. Lockshin","doi":"10.3389/fceld.2023.1197400","DOIUrl":"https://doi.org/10.3389/fceld.2023.1197400","url":null,"abstract":"The concept of biological cell death—that is, cell death that is neither accidental nor chaotic—has existed and has been obvious since at least the beginning of the 20th C, but it was noticed by other than specialists apt choices of words that caught the spirit of the time, “programmed cell death” and “apoptosis” caught the attention of a wider range of scientists. Then, by the early 1990s the recognition of at least two genes that were important to cancer and other diseases by controlling cell death (p53, Bcl-2, and Fas); recognition that cell death could be controlled by a highly conserved family of proteases; and the development of rapid and easy means of measuring cell death, led to the explosion of the field as a subject of research. Today we recognize many variations on the theme of biological cell death, but many mysteries remain. The most important of these remaining mysteries is that we recognize many of the penultimate and ultimate steps to kill cells, but it is rarely clear how and why these steps are activated. Most likely they are activated by an interaction of several metabolic steps, but we will need more high-powered analysis to determine how this interaction functions.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"14 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72557402","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

Multifaceted promotion of apoptosis by acetylcholinesterase 乙酰胆碱酯酶多方面促进细胞凋亡

Frontiers in cell death Pub Date : 2023-04-17 DOI: 10.3389/fceld.2023.1169966

Debbra Y. Knorr, D. Demirbas, R. Heinrich

{"title":"Multifaceted promotion of apoptosis by acetylcholinesterase","authors":"Debbra Y. Knorr, D. Demirbas, R. Heinrich","doi":"10.3389/fceld.2023.1169966","DOIUrl":"https://doi.org/10.3389/fceld.2023.1169966","url":null,"abstract":"Elevated expression of acetylcholinesterase (AChE) is a common characteristic of apoptotic cells in both invertebrate and vertebrate species. While increased levels of acetylcholinesterase sensitize cells to apoptogenic stimuli, its absence or pharmacological inactivation interferes with apoptotic cell death. acetylcholinesterase may exert its pro-apoptotic function directly as an integral component of the apoptotic molecular machinery or indirectly by limiting the availability of receptor ligands and structural binding partners that promote cell survival under non-apoptogenic conditions. acetylcholinesterase promotes formation of the apoptosome and degrades DNA after nuclear accumulation. Its esterase activity limits the availability of acetylcholine as ligand for cell membrane-located nicotinic and muscarinic ACh-receptors and mitochondrial nicotinic ACh-receptors that normally support vital physiological states. Studies on insects suggest, that cytokine-activated cell-protective pathways may suppress acetylcholinesterase overexpression under apoptogenic conditions to prevent apoptotic cell death. We provide an overview of studies on various organisms and cell types that summarizes the contribution of acetylcholinesterase to the progress of apoptosis via multiple mechanisms.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77340781","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

Non-lethal roles of the initiator caspase Dronc in Drosophila caspase Dronc在果蝇中的非致死性作用

Frontiers in cell death Pub Date : 2023-04-06 DOI: 10.3389/fceld.2023.1184041

Daniel Domínguez, Yun Fan

引用次数: 0

From TNF-induced signaling to NADPH oxidase enzyme activity: Methods to investigate protein complexes involved in regulated cell death modalities 从tnf诱导的信号传导到NADPH氧化酶活性:研究参与调节细胞死亡方式的蛋白质复合物的方法

Frontiers in cell death Pub Date : 2023-04-05 DOI: 10.3389/fceld.2023.1127330

Maria Ladik, Hana Valenta, M. Erard, P. Vandenabeele, Franck B. Riquet

{"title":"From TNF-induced signaling to NADPH oxidase enzyme activity: Methods to investigate protein complexes involved in regulated cell death modalities","authors":"Maria Ladik, Hana Valenta, M. Erard, P. Vandenabeele, Franck B. Riquet","doi":"10.3389/fceld.2023.1127330","DOIUrl":"https://doi.org/10.3389/fceld.2023.1127330","url":null,"abstract":"The formation of molecular complexes is a key feature of intracellular signaling pathways which governs to the initiation and execution of dedicated cellular processes. Tumor Necrosis Factor (TNF) and Reactive Oxygen Species (ROS) function as signaling molecules and are both involved in balancing cell fate decision between cell survival or cell demise. As master regulators of cell signaling, they are also instrumental in controlling various cellular processes towards tissue homeostasis, innate immunity and inflammation. Interestingly, TNF and ROS are interlinked and involved in regulating each other’s production via the engagement of molecular signaling complexes. This relationship calls for detailed reviewing of both TNF-induced and ROS-producing molecular complexes in the context of regulated cell death (RCD) modalities. Here, we outline biotechnological approaches that were used to investigate the TNF- and, concerning ROS, the NADPH oxidase-related molecular complexes with an emphasis on different regulated cell death modalities. This systematic review highlights how the cell death field has benefited from both biochemical and live-cell fluorescence imaging approaches. This knowledge and established workflows are highly generalizable, can be of a broader use for any protein-complex studies, and well suited for addressing new challenges in signaling dynamics. These will help understand molecular signaling complexes as ensembles organized into signaling platforms, most likely the key sites of signaling dynamics integration toward cell fate regulation.","PeriodicalId":73072,"journal":{"name":"Frontiers in cell death","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75368004","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

Regulators mount up: the metabolic roles of apoptotic proteins. 凋亡蛋白的新陈代谢作用。

Frontiers in cell death Pub Date : 2023-01-01 Epub Date: 2023-07-03 DOI: 10.3389/fceld.2023.1223926

James H Schofield, Zachary T Schafer

引用次数: 0