scholarly journals Autophagic Cell Death During Development – Ancient and Mysterious

2021 ◽  
Vol 9 ◽  
Author(s):  
Lawrence M. Schwartz
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Membrane Vesicles ◽  
Autophagic Cell Death ◽  
Extensive Literature ◽  
Distinct Process ◽  
Dependent Cell ◽  
Mediate Cell

While cell death is a normal and essential component of development and homeostasis, dysregulation of this process underlies most human diseases, including cancer, autoimmunity and neurodegeneration. The best characterized mechanism for cell death is apoptosis, although some cells die by a distinct process known as autophagy-dependent cell death (ADCD). Autophagy is mediated by the formation of double membrane vesicles that contain protein aggregates, damaged organelles like mitochondria, and bulk cytoplasm, which then fuse with lysosomes to degrade and recycle their contents. Autophagy is typically viewed as an adaptive process that allows cells to survive stresses like nutrient deprivation, although increasing evidence suggests that it may also mediate cell death during development and pathogenesis. An aggressive form of autophagy termed autosis has been described in cells following either ischemia/reperfusion injury or in response to autophagy-inducing proteins like Tat-Beclin 1. Despite an extensive literature on autophagic cell death in a variety of contexts, there are still fundamental gaps in our understanding of this process. As examples: Does autophagy directly kill cells and if so how? Is ADCD activated concurrently when cells are triggered to die via apoptosis? And is ADCD essentially a more protracted version of autosis or a distinct pathway? The goal of this mini-review is to summarize the field and to identify some of the major gaps in our knowledge. Understanding the molecular mechanisms that mediate ADCD will not only provide new insights into development, they may facilitate the creation of better tools for both the diagnostics and treatment of disease.

Propofol protects the autophagic cell death induced by the ischemia/reperfusion injury in rats

2010 ◽  
Vol 30 (5) ◽  
pp. 455-460 ◽  
Author(s):  
Hae Sook Noh ◽  
Il Woo Shin ◽  
Ji Hye Ha ◽  
Young-Sool Hah ◽  
Seon Mi Baek ◽  
...  
Keyword(s):  
Cell Death ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Autophagic Cell Death

scholarly journals Molecular Mechanisms of Ferroptosis and Its Roles in Hematologic Malignancies

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Zhao ◽  
Zineng Huang ◽  
Hongling Peng
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Hematological Malignancies ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lipid Peroxide ◽  
Kidney Injury ◽  
Hematologic Malignancies ◽  
Regulated Cell Death ◽  
Normal Metabolism

Cell death is essential for the normal metabolism of human organisms. Ferroptosis is a unique regulated cell death (RCD) mode characterized by excess accumulation of iron-dependent lipid peroxide and reactive oxygen species (ROS) compared with other well-known programmed cell death modes. It has been currently recognized that ferroptosis plays a rather important role in the occurrence, development, and treatment of traumatic brain injury, stroke, acute kidney injury, liver damage, ischemia–reperfusion injury, tumor, etc. Of note, ferroptosis may be explained by the expression of various molecules and signaling components, among which iron, lipid, and amino acid metabolism are the key regulatory mechanisms of ferroptosis. Meanwhile, tumor cells of hematological malignancies, such as leukemia, lymphoma, and multiple myeloma (MM), are identified to be sensitive to ferroptosis. Targeting potential regulatory factors in the ferroptosis pathway may promote or inhibit the disease progression of these malignancies. In this review, a systematic summary was conducted on the key molecular mechanisms of ferroptosis and the current potential relationships of ferroptosis with leukemia, lymphoma, and MM. It is expected to provide novel potential therapeutic approaches and targets for hematological malignancies.

scholarly journals The Link Between Ferroptosis and Cardiovascular Diseases: A Novel Target for Treatment

2021 ◽  
Vol 8 ◽  
Author(s):  
Huilin Hu ◽  
Yunqing Chen ◽  
Lele Jing ◽  
Changlin Zhai ◽  
Liang Shen
Keyword(s):  
Cell Death ◽  
Cardiovascular Diseases ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Current Status ◽  
Mitochondrial Activity ◽  
Potential Therapeutic Target ◽  
Dependent Cell ◽  
Novel Target ◽  
And Function

Ferroptosis is an iron-dependent cell death, which is characterized by iron overload and lipid peroxidation. Ferroptosis is distinct from apoptosis, necroptosis, autophagy, and other types of cell death in morphology and function. Ferroptosis is regulated by a variety of factors and controlled by several mechanisms, including mitochondrial activity and metabolism of iron, lipid, and amino acids. Accumulating evidence shows that ferroptosis is closely related to a majority of cardiovascular diseases (CVDs), including cardiomyopathy, myocardial infarction, ischemia/reperfusion injury, heart failure, and atherosclerosis. This review summarizes the current status of ferroptosis and discusses ferroptosis as a potential therapeutic target for CVDs.

Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia/reperfusion injury

2021 ◽  
Author(s):  
Aleksandra Stamenkovic ◽  
Kimberley A. O'Hara ◽  
David C. Nelson ◽  
Thane G Maddaford ◽  
Andrea L. Edel ◽  
...  
Keyword(s):  
Cell Death ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Calcium Transients ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Mediate Cell ◽  
Myocardial Ischemia Reperfusion ◽  
Vehicle Treated Control

Myocardial ischemia/reperfusion (I/R) injury increases the generation of oxidized phosphatidylcholines (OxPCs) which results in cell death. However, the mechanism by which OxPCs mediate cell death is largely unknown. The aim of this study was to determine the mechanisms by which OxPC triggers cardiomyocyte cell death during reperfusion injury. Cardiomyocyte viability, bioenergetic response and calcium transients were determined in the presence of OxPCs. Fragmented OxPCs resulted in a decrease in cell viability with POVPC and PONPC having the most potent cardiotoxic effect in both a concentration and time dependent manner (P<0.05). POVPC and PONPC also caused a significant decrease in Ca2+ transients and net contraction in isolated cardiomyocytes compared to vehicle treated control cells (P<0.05). PONPC depressed maximal respiration rate (p<0.01; 54%) and spare respiratory capacity (p<0.01; 54.5%). Notably, neither caspase 3 activation or TUNEL staining was observed in cells treated with either POVPC or PONPC. Further, cardiac myocytes treated with OxPCs were indistinguishable from vehicle treated control cells with respect to nuclear HMGB1 activity. Glutathione peroxidase 4 activity was markedly suppressed in cardiomyocytes treated with POVPC and PONPC. Importantly, cell death induced by OxPCs could be suppressed E06 Ab, directed against OxPCs or by ferrostatin. The findings of the present study suggest that OxPCs disrupt mitochondrial bioenergetics, calcium transients and provoke wide spread cell death through ferroptosis during I/R. Neutralization of OxPC with E06 or with ferrostatin-1 prevents cell death during reperfusion. Our study demonstrates a novel signaling pathway that operationally links generation of OxPC during cardiac I/R to ferroptosis.

scholarly journals Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Yu ◽  
Yuan Yan ◽  
Fanglin Niu ◽  
Yajun Wang ◽  
Xueyi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cardiovascular Diseases ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lipid Peroxide ◽  
Nuclear Condensation ◽  
Redox Active ◽  
Dependent Cell

AbstractFerroptosis, a recently identified and iron-dependent cell death, differs from other cell death such as apoptosis, necroptosis, pyroptosis, and autophagy-dependent cell death. This form of cell death does not exhibit typical morphological and biochemical characteristics, including cell shrinkage, mitochondrial fragmentation, nuclear condensation. The dysfunction of lipid peroxide clearance, the presence of redox-active iron as well as oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids are three essential features of ferroptosis. Iron metabolism and lipid peroxidation signaling are increasingly recognized as central mediators of ferroptosis. Ferroptosis plays an important role in the regulation of oxidative stress and inflammatory responses. Accumulating evidence suggests that ferroptosis is implicated in a variety of cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure, indicating that targeting ferroptosis will present a novel therapeutic approach against cardiovascular diseases. Here, we provide an overview of the features, process, function, and mechanisms of ferroptosis, and its increasingly connected relevance to oxidative stress, inflammation, and cardiovascular diseases.

scholarly journals Roles of pyroptosis in myocardial ischemia/reperfusion injury diseases

2019 ◽  
Author(s):  
Shupeng Shi ◽  
Haoran Zhang ◽  
Wenzhe Gao ◽  
Moussa Ide Nasser ◽  
Jie Shen ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Research Progress ◽  
Modern World ◽  
Myocardial Tissue ◽  
Molecular Signaling

Ischemia-reperfusion injury (IRI) occurred when an organ lost its blood supply in a short time, and then the perfusion was restored automatically or iatrogenically, leading to a burst of reactive oxygen species (ROS) from mitochondria. It is common in the clinic, and lead to deterioration, even death, so an exploratory examination of the mechanism of ischemia-reperfusion injury is of great significance. Among the most common and fatal types of IR in myocardial tissue, myocardial IRI is one of the most fatal diseases in the modern world. The cellular and molecular mechanisms of IRI mainly include calcium overload, oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, energy metabolic disorders, neutrophil infiltration, cardiomyocyte autophagy, and apoptosis, etc. The main pathogenesis of IRI is programmed cell death, of which apoptosis is the most deeply studied processes. However, pyroptosis is a highly inflammatory form of programmed cell death (PCD), which depends on the activation of the caspase cascade and inflammatory mediators, which have been thought to be involved in the processes of IRI. Ptosis has been referred to as a pattern. PCD with apoptosis characteristics Necrosis. It’s stimulated by molecular signaling pathways similar to apoptosis, mainly including Caspase. The research progress in recent years is presented in this review. Among them, myocardial tissue and so on provide a theoretical basis for the burning organ system in I/R injury and provide theoretical practice for the clinical research of reducing ischemia-reperfusion injury.

scholarly journals Iron in Cardiovascular Disease: Challenges and Potentials

2021 ◽  
Vol 8 ◽  
Author(s):  
Shizhen Li ◽  
Xiangyu Zhang
Keyword(s):  
Cardiovascular Disease ◽  
Cell Death ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Iron Chelation ◽  
Medical Intervention ◽  
Atherosclerotic Cardiovascular Disease ◽  
Dependent Cell ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Iron is essential for many biological processes. Inadequate or excess amount of body iron can result in various pathological consequences. The pathological roles of iron in cardiovascular disease (CVD) have been intensively studied for decades. Convincing data demonstrated a detrimental effect of iron deficiency in patients with heart failure and pulmonary arterial hypertension, but it remains unclear for the pathological roles of iron in other cardiovascular diseases. Meanwhile, ferroptosis is an iron-dependent cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been reported in several CVDs, namely, cardiomyopathy, atherosclerotic cardiovascular disease, and myocardial ischemia/reperfusion injury. Iron chelation therapy seems to be an available strategy to ameliorate iron overload-related disorders. It is still a challenge to accurately clarify the pathological roles of iron in CVD and search for effective medical intervention. In this review, we aim to summarize the pathological roles of iron in CVD, and especially highlight the potential mechanism of ferroptosis in these diseases.

scholarly journals Roles of pyroptosis in myocardial ischemia/reperfusion injury diseases

2019 ◽  
Author(s):  
Shupeng Shi ◽  
Haoran Zhang ◽  
Wenzhe Gao ◽  
Moussa Ide Nasser ◽  
Jie Shen ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Research Progress ◽  
Modern World ◽  
Myocardial Tissue ◽  
Molecular Signaling

Ischemia-reperfusion injury (IRI) occurred when an organ lost its blood supply in a short time, and then the perfusion was restored automatically or iatrogenically, leading to a burst of reactive oxygen species (ROS) from mitochondria. It is common in the clinic, and lead to deterioration, even death, so an exploratory examination of the mechanism of ischemia-reperfusion injury is of great significance. Among the most common and fatal types of IR in myocardial tissue, myocardial IRI is one of the most fatal diseases in the modern world. The cellular and molecular mechanisms of IRI mainly include calcium overload, oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, energy metabolic disorders, neutrophil infiltration, cardiomyocyte autophagy, and apoptosis, etc. The main pathogenesis of IRI is programmed cell death, of which apoptosis is the most deeply studied processes. However, pyroptosis is a highly inflammatory form of programmed cell death (PCD), which depends on the activation of the caspase cascade and inflammatory mediators, which have been thought to be involved in the processes of IRI. Ptosis has been referred to as a pattern. PCD with apoptosis characteristics Necrosis. It’s stimulated by molecular signaling pathways similar to apoptosis, mainly including Caspase. The research progress in recent years is presented in this review. Among them, myocardial tissue and so on provide a theoretical basis for the burning organ system in I/R injury and provide theoretical practice for the clinical research of reducing ischemia-reperfusion injury.

scholarly journals microRNA-377 Signaling Modulates Anticancer Drug-Induced Cardiotoxicity in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
John Henderson ◽  
Praveen K. Dubey ◽  
Mallikarjun Patil ◽  
Sarojini Singh ◽  
Shubham Dubey ◽  
...  
Keyword(s):  
Cell Death ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Drug Induced ◽  
Chemotherapy Agent

Doxorubicin (DOX, an anthracycline) is a widely used chemotherapy agent against various forms of cancer; however, it is also known to induce dose-dependent cardiotoxicity leading to adverse complications. Investigating the underlying molecular mechanisms and strategies to limit DOX-induced cardiotoxicity might have potential clinical implications. Our previous study has shown that expression of microRNA-377 (miR-377) increases in cardiomyocytes (CMs) after cardiac ischemia-reperfusion injury in mice, but its specific role in DOX-induced cardiotoxicity has not been elucidated. In the present study, we investigated the effect of anti-miR-377 on DOX-induced cardiac cell death, remodeling, and dysfunction. We evaluated the role of miR-377 in CM apoptosis, its target analysis by RNA sequencing, and we tested the effect of AAV9-anti-miR-377 on DOX-induced cardiotoxicity and mortality. DOX administration in mice increases miR-377 expression in the myocardium. miR-377 inhibition in cardiomyocyte cell line protects against DOX-induced cell death and oxidative stress. Furthermore, RNA sequencing and Gene Ontology (GO) analysis revealed alterations in a number of cell death/survival genes. Intriguingly, we observed accelerated mortality and enhanced myocardial remodeling in the mice pretreated with AAV9-anti-miR-377 followed by DOX administration as compared to the AAV9-scrambled-control-pretreated mice. Taken together, our data suggest that in vitro miR-377 inhibition protects against DOX-induced cardiomyocyte cell death. On the contrary, in vivo administration of AAV9-anti-miR-377 increases mortality in DOX-treated mice.

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