scholarly journals The Role of Ferroptosis in Cardiovascular Disease and Its Therapeutic Significance

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhenzhen Chen ◽  
Youyou Yan ◽  
Chao Qi ◽  
Jia Liu ◽  
Longbo Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Damage ◽  
Regulated Cell Death ◽  
Cardiac Pathophysiology ◽  
Cause Of Deaths ◽  
New Type ◽  
The Relationship ◽  
Infarction Heart ◽  
Related Pathway

Cardiovascular diseases (CVDs) are the leading cause of deaths worldwide with regulated cell death playing an important role in cardiac pathophysiology. However, the classical mode of cell death cannot fully explain the occurrence and development of heart disease. In recent years, much research has been performed on ferroptosis, a new type of cell death that causes cell damage and contributes to the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In this review, we discuss the role of different organelles in ferroptosis and also focus on the relationship between autophagy and ferroptosis. Additionally, we describe the specific mechanism by which ferroptosis contributes to the development of CVD. Finally, we summarize the current research on ferroptosis-related pathway inhibitors and the applications of clinically beneficial cardiovascular drugs.

scholarly journals Novel insights on targeting ferroptosis in cancer therapy

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Sipeng Zuo ◽  
Jie Yu ◽  
Hui Pan ◽  
Linna Lu
Keyword(s):  
Cell Death ◽  
Heart Disease ◽  
Cancer Therapy ◽  
Alzheimer Disease ◽  
Cellular Structure ◽  
Redox Balance ◽  
Regulated Cell Death ◽  
Novel Theory ◽  
The Relationship

Abstract Ferroptosis belongs to a novel form of regulated cell death. It is characterized by iron dependence, destruction of intracellular redox balance and non-apoptosis. And cellular structure and molecules level changes also occur abnormally during ferroptosis. It has been proved that ferroptosis exist widespreadly in many diseases, such as heart disease, brain damage or alzheimer disease. At the same time, the role of ferroptosis in cancer cannot be underestimated. More and more indications have told that ferroptosis is becoming a powerful weapon against cancer. In addition, therapies rely on ferroptosis have been applied to the clinic. Therefore, it is necessary to understand this newly discovered form of cell death and its connection with cancer. This review summarizes the mechanism of ferroptosis, ferroptosis inducers based on different targets and inspection methods. At last, we analyzed the relationship between ferroptosis and malignancies, in order to provide a novel theory basis for cancer treatment.

scholarly journals Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1505 ◽  
Author(s):  
Anna Martina Battaglia ◽  
Roberta Chirillo ◽  
Ilenia Aversa ◽  
Alessandro Sacco ◽  
Francesco Costanzo ◽  
...  
Keyword(s):  
Cell Death ◽  
Mitochondrial Morphology ◽  
Oxygen Species ◽  
Severe Damage ◽  
Master Regulators ◽  
Regulated Cell Death ◽  
New Strategy ◽  
Metabolic Imbalance ◽  
New Type

Ferroptosis is a new type of oxidative regulated cell death (RCD) driven by iron-dependent lipid peroxidation. As major sites of iron utilization and master regulators of oxidative metabolism, mitochondria are the main source of reactive oxygen species (ROS) and, thus, play a role in this type of RCD. Ferroptosis is, indeed, associated with severe damage in mitochondrial morphology, bioenergetics, and metabolism. Furthermore, dysregulation of mitochondrial metabolism is considered a biochemical feature of neurodegenerative diseases linked to ferroptosis. Whether mitochondrial dysfunction can, per se, initiate ferroptosis and whether mitochondrial function in ferroptosis is context-dependent are still under debate. Cancer cells accumulate high levels of iron and ROS to promote their metabolic activity and growth. Of note, cancer cell metabolic rewiring is often associated with acquired sensitivity to ferroptosis. This strongly suggests that ferroptosis may act as an adaptive response to metabolic imbalance and, thus, may constitute a new promising way to eradicate malignant cells. Here, we review the current literature on the role of mitochondria in ferroptosis, and we discuss opportunities to potentially use mitochondria-mediated ferroptosis as a new strategy for cancer therapy.

scholarly journals A Bibliometric Analysis of Pyroptosis From 2001 to 2021

2021 ◽  
Vol 12 ◽  
Author(s):  
Dan Ma ◽  
Bin Yang ◽  
Baoyi Guan ◽  
Luxia Song ◽  
Qiyu Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Bibliometric Analysis ◽  
Future Research ◽  
Pyrin Domain ◽  
The Future ◽  
The Usa ◽  
The Relationship ◽  
Related Pathway ◽  
Receptor Family

BackgroundPyroptosis is a new programmed cell death discovered in recent years. Pyroptosis plays an important role in various diseases. Nevertheless, there are few bibliometric analysis systematically studies this field. We aimed to visualize the research hotspots and trends of pyroptosis using a bibliometric analysis to help understand the future development of basic and clinical research.MethodsThe articles and reviews regarding pyroptosis were culled from Web of Science Core Collection. Countries, institutions, authors, references and keywords in this field were visually analyzed by using CtieSpace and VOSviewer software.ResultsA total of 2845 articles and reviews were included. The number of articles regarding pyroptosis significantly increased yearly. These publications mainly come from 70 countries led by China and the USA and 418 institutions. We identified 605 authors, among which Thirumaladevi Kanneganti had the most significant number of articles, and Shi JJ was co-cited most often. Frontiers in immunology was the journal with the most studies, and Nature was the most commonly cited journal. After analysis, the most common keywords are nod like receptor family pyrin domain containing 3 inflammasome, apoptosis, cell death, gasdermin D, mechanism, caspase-1, and others are current and developing areas of study.ConclusionResearch on the pyroptosis is flourishing. Cooperation and exchanges between countries and institutions must be strengthened in the future. The related pathway mechanism of pyroptosis, the relationship between pyroptosis and other types of programmed cell deaths as well as the role of pyroptosis in various diseases have been the focus of current research and developmental trends in the future research.

scholarly journals Role of Hypoxia-Mediated Autophagy in Tumor Cell Death and Survival

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 533
Author(s):  
Rania F. Zaarour ◽  
Bilal Azakir ◽  
Edries Y. Hajam ◽  
Husam Nawafleh ◽  
Nagwa A. Zeinelabdin ◽  
...  
Keyword(s):  
Cell Death ◽  
Type I ◽  
Dependent Manner ◽  
Destruction Process ◽  
Tumor Cell Death ◽  
Complex Regulation ◽  
Cancer Immunotherapies ◽  
The Relationship ◽  
Shed Light

Programmed cell death or type I apoptosis has been extensively studied and its contribution to the pathogenesis of disease is well established. However, autophagy functions together with apoptosis to determine the overall fate of the cell. The cross talk between this active self-destruction process and apoptosis is quite complex and contradictory as well, but it is unquestionably decisive for cell survival or cell death. Autophagy can promote tumor suppression but also tumor growth by inducing cancer-cell development and proliferation. In this review, we will discuss how autophagy reprograms tumor cells in the context of tumor hypoxic stress. We will illustrate how autophagy acts as both a suppressor and a driver of tumorigenesis through tuning survival in a context dependent manner. We also shed light on the relationship between autophagy and immune response in this complex regulation. A better understanding of the autophagy mechanisms and pathways will undoubtedly ameliorate the design of therapeutics aimed at targeting autophagy for future cancer immunotherapies.

scholarly journals Language in social reproduction: Sociolinguistics and sociosemiotics

2009 ◽  
Vol 37 (1/2) ◽  
pp. 43-81
Author(s):  
Patrizia Calefato
Keyword(s):  
Social Reproduction ◽  
Social Dimension ◽  
The Social ◽  
The Sixties ◽  
Roman Jakobson ◽  
New Type ◽  
General Linguistics ◽  
Definition Of ◽  
The Relationship

This paper focuses on the semiotic foundations of sociolinguistics. Starting from the definition of “sociolinguistics” given by the philosopher Adam Schaff, the paper examines in particular the notion of “critical sociolinguistics” as theorized by the Italian semiotician Ferruccio Rossi-Landi. The basis of the social dimension of language are to be found in what Rossi-Landi calls “social reproduction” which regards both verbal and non-verbal signs. Saussure’s notion of langue can be considered in this way, with reference not only to his Course of General Linguistics, but also to his Harvard Manuscripts.The paper goes on trying also to understand Roland Barthes’s provocative definition of semiology as a part of linguistics (and not vice-versa) as well as developing the notion of communication-production in this perspective. Some articles of Roman Jakobson of the sixties allow us to reflect in a manner which we now call “socio-semiotic” on the processes of transformation of the “organic” signs into signs of a new type, which articulate the relationship between organic and instrumental. In this sense, socio-linguistics is intended as being sociosemiotics, without prejudice to the fact that the reference area must be human, since semiotics also has the prerogative of referring to the world of non-human vital signs.Socio-linguistics as socio-semiotics assumes the role of a “frontier” science, in the dual sense that it is not only on the border between science of language and the anthropological and social sciences, but also that it can be constructed in a movement of continual “crossing frontiers” and of “contamination” between languages and disciplinary environments.

scholarly journals The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4576
Author(s):  
Hung-Yu Lin ◽  
Hui-Wen Ho ◽  
Yen-Hsiang Chang ◽  
Chun-Jui Wei ◽  
Pei-Yi Chu
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Drug Resistant ◽  
Therapeutic Targeting ◽  
The Past ◽  
Regulated Cell Death ◽  
Common Malignancy

Breast cancer (BC) is the most common malignancy among women worldwide. The discovery of regulated cell death processes has enabled advances in the treatment of BC. In the past decade, ferroptosis, a new form of iron-dependent regulated cell death caused by excessive lipid peroxidation has been implicated in the development and therapeutic responses of BC. Intriguingly, the induction of ferroptosis acts to suppress conventional therapy-resistant cells, and to potentiate the effects of immunotherapy. As such, pharmacological or genetic modulation targeting ferroptosis holds great potential for the treatment of drug-resistant cancers. In this review, we present a critical analysis of the current understanding of the molecular mechanisms and regulatory networks involved in ferroptosis, the potential physiological functions of ferroptosis in tumor suppression, its potential in therapeutic targeting, and explore recent advances in the development of therapeutic strategies for BC.

scholarly journals Insight into the Double-Edged Role of Ferroptosis in Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1790
Author(s):  
Lei Zhang ◽  
Ruohan Jia ◽  
Huizhen Li ◽  
Huarun Yu ◽  
Keke Ren ◽  
...  
Keyword(s):  
Cell Death ◽  
Digestive System ◽  
Kidney Injury ◽  
Oxygen Species ◽  
Disease Treatment ◽  
The Relationship ◽  
Insight Into ◽  
New Strategies ◽  
Research Hotspots

Ferroptosis, a newly described type of iron-dependent programmed cell death that is distinct from apoptosis, necroptosis, and other types of cell death, is involved in lipid peroxidation (LP), reactive oxygen species (ROS) production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury, cancer, hepatic fibrosis, Parkinson’s disease, and Alzheimer’s disease. Therefore, ferroptosis has become one of the research hotspots for disease treatment and attracted extensive attention in recent years. This review mainly summarizes the relationship between ferroptosis and various diseases classified by the system, including the urinary system, digestive system, respiratory system, nervous system. In addition, the role and molecular mechanism of multiple inhibitors and inducers for ferroptosis are further elucidated. A deeper understanding of the relationship between ferroptosis and multiple diseases may provide new strategies for researching diseases and drug development based on ferroptosis.

scholarly journals Bcl2 inhibits apoptosis associated with terminal differentiation of HL- 60 myeloid leukemia cells

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2261-2267 ◽  
Author(s):  
L Naumovski ◽  
ML Cleary
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Myeloid Cells ◽  
Terminal Differentiation ◽  
Retroviral Gene Transfer ◽  
Protein Levels ◽  
All Trans Retinoic Acid ◽  
Bcl2 Protein ◽  
The Relationship

Abstract The Bcl2 protein inhibits apoptosis (programmed cell death) induced by a variety of noxious stimuli. However, relatively little is known about its effect on apoptosis that occurs after terminal differentiation. Bcl2 protein levels decrease during differentiation of myeloid cells into granulocytes that subsequently undergo apoptosis, but the potential role of Bcl2 in coupling survival and differentiation remains undefined. To ascertain the relationship between decreasing Bcl2 levels and the onset of apoptosis in differentiating myeloid cells, Bcl2 was hyperexpressed in the HL-60 cell line after retroviral gene transfer. After treatment of HL-60/BCL2 cells with all-trans retinoic acid or phorbol myristic acid, Bcl2 levels did not decrease as in normal HL-60 cells but, rather, increased because of activation of the viral promoter. Differentiation of the Bcl2-overexpressing cells was similar to that of normal HL-60 cells, but they showed little evidence for apoptosis and had a prolonged survival. These studies show that the survival-enhancing properties of Bcl2 counteract programmed cell death that accompanies terminal differentiation; however, Bcl2 has no significant effect on differentiation itself, suggesting that apoptosis and differentiation are regulated independently in myeloid cells.

scholarly journals The emerging role of ferroptosis in non-cancer liver diseases: hype or increasing hope?

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Lihong Mao ◽  
Tianming Zhao ◽  
Yan Song ◽  
Lin Lin ◽  
Xiaofei Fan ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Diseases ◽  
Therapeutic Strategy ◽  
Kidney Injury ◽  
Hepatic Disease ◽  
Therapeutic Concept ◽  
Regulated Cell Death ◽  
Dependent Form ◽  
Molecular Machinery

Abstract Ferroptosis is an iron- and lipotoxicity-dependent form of regulated cell death (RCD). It is morphologically and biochemically distinct from characteristics of other cell death. This modality has been intensively investigated in recent years due to its involvement in a wide array of pathologies, including cancer, neurodegenerative diseases, and acute kidney injury. Dysregulation of ferroptosis has also been linked to various liver diseases and its modification may provide a hopeful and attractive therapeutic concept. Indeed, targeting ferroptosis may prevent the pathophysiological progression of several liver diseases, such as hemochromatosis, nonalcoholic steatohepatitis, and ethanol-induced liver injury. On the contrary, enhancing ferroptosis may promote sorafenib-induced ferroptosis and pave the way for combination therapy in hepatocellular carcinoma. Glutathione peroxidase 4 (GPx4) and system xc− have been identified as key players to mediate ferroptosis pathway. More recently diverse signaling pathways have also been observed. The connection between ferroptosis and other forms of RCD is intricate and compelling, where discoveries in this field advance our understanding of cell survival and fate. In this review, we summarize the central molecular machinery of ferroptosis, describe the role of ferroptosis in non-cancer hepatic disease conditions and discuss the potential to manipulate ferroptosis as a therapeutic strategy.

scholarly journals Excessive phospholipid peroxidation distinguishes ferroptosis from other cell death modes including pyroptosis

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Bartosz Wiernicki ◽  
Hanne Dubois ◽  
Yulia Y. Tyurina ◽  
Behrouz Hassannia ◽  
Hülya Bayir ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
The Other ◽  
Strong Increase ◽  
Oxygen Species ◽  
Membrane Rupture ◽  
Regulated Cell Death ◽  
Phospholipid Peroxidation ◽  
Differential Involvement

Abstract Lipid peroxidation (LPO) drives ferroptosis execution. However, LPO has been shown to contribute also to other modes of regulated cell death (RCD). To clarify the role of LPO in different modes of RCD, we studied in a comprehensive approach the differential involvement of reactive oxygen species (ROS), phospholipid peroxidation products, and lipid ROS flux in the major prototype modes of RCD viz. apoptosis, necroptosis, ferroptosis, and pyroptosis. LC-MS oxidative lipidomics revealed robust peroxidation of three classes of phospholipids during ferroptosis with quantitative predominance of phosphatidylethanolamine species. Incomparably lower amounts of phospholipid peroxidation products were found in any of the other modes of RCD. Nonetheless, a strong increase in lipid ROS levels was detected in non-canonical pyroptosis, but only during cell membrane rupture. In contrast to ferroptosis, lipid ROS apparently was not involved in non-canonical pyroptosis execution nor in the release of IL-1β and IL-18, while clear dependency on CASP11 and GSDMD was observed. Our data demonstrate that ferroptosis is the only mode of RCD that depends on excessive phospholipid peroxidation for its cytotoxicity. In addition, our results also highlight the importance of performing kinetics and using different methods to monitor the occurrence of LPO. This should open the discussion on the implication of particular LPO events in relation to different modes of RCD.

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