scholarly journals Ferroptosis and Its Multifaceted Roles in Cerebral Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Yongfa Zhang ◽  
Xiaoyang Lu ◽  
Bai Tai ◽  
Weijia Li ◽  
Tao Li
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Iron Overload ◽  
Hemorrhagic Stroke ◽  
Lipid Peroxides ◽  
Cerebral Stroke ◽  
Intracellular Iron ◽  
Biological Features ◽  
Pathophysiological Process ◽  
Regulated Cell Death

Ferroptosis is a unique regulated cell death defined by the intracellular iron overload and distinct biological features compared with other well-known programmed cell death. Ferroptosis can be triggered by many causes including decreased expression of glutathione (GSH), inhibition of the function of glutathione-dependent peroxidase 4 (GPX4), and system xc–, all of which finally lead to the over-accumulation of lipid peroxides in the cell. Ferroptosis has been reported to play an important role in the pathophysiological process of various cancers. In recent years, much evidence also proved that ferroptosis is involved in the progress of cerebral stroke. In this review, we summarized the characteristics of ferroptosis and the potential relationship between ferroptosis and ischemic and hemorrhagic stroke, to provide new targets and ideas for the therapy of stroke.

scholarly journals Ferroptosis-mediated Crosstalk in the Tumor Microenvironment Implicated in Cancer Progression and Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yini Liu ◽  
Chunyan Duan ◽  
Rongyang Dai ◽  
Yi Zeng
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Lipid Peroxides ◽  
Antioxidant Systems ◽  
Biological Processes ◽  
The Novel ◽  
Regulated Cell Death ◽  
Novel Therapeutic Strategies

Ferroptosis is a recently recognized form of non-apoptotic regulated cell death and usually driven by iron-dependent lipid peroxidation and has arisen to play a significant role in cancer biology. Distinct from other types of cell death in morphology, genetics, and biochemistry, ferroptosis is characterized by the accumulation of lipid peroxides and lethal reactive oxygen species controlled by integrated oxidant and antioxidant systems. Increasing evidence indicates that a variety of biological processes, including amino acid, iron, lactate, and lipid metabolism, as well as glutathione, phospholipids, NADPH, and coenzyme Q10 biosynthesis, are closely related to ferroptosis sensitivity. Abnormal ferroptotic response may modulate cancer progression by reprogramming the tumor microenvironment (TME). The TME is widely associated with tumor occurrence because it is the carrier of tumor cells, which interacts with surrounding cells through the circulatory and the lymphatic system, thus influencing the development and progression of cancer. Furthermore, the metabolism processes play roles in maintaining the homeostasis and evolution of the TME. Here, this review focuses on the ferroptosis-mediated crosstalk in the TME, as well as discussing the novel therapeutic strategies for cancer treatment.

Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors

2018 ◽  
Vol 503 (1) ◽  
pp. 297-303 ◽  
Author(s):  
Shenglin Fang ◽  
Xiaonan Yu ◽  
Haoxuan Ding ◽  
Jianan Han ◽  
Jie Feng
Keyword(s):  
Cell Death ◽  
Iron Overload ◽  
Intracellular Iron

scholarly journals Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1677
Author(s):  
Anna Maria Fratta Pasini ◽  
Chiara Stranieri ◽  
Domenico Girelli ◽  
Fabiana Busti ◽  
Luciano Cominacini
Keyword(s):  
Reactive Oxygen Species ◽  
Fatty Acids ◽  
Cell Death ◽  
Cardiogenic Shock ◽  
Molecular Mechanisms ◽  
Lipid Peroxides ◽  
Oxygen Species ◽  
Intracellular Iron ◽  
Multiple Organs ◽  
Respiratory Pathology

Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature of myocardial and kidney ferroptosis, a novel, iron-dependent programmed cell death. The term ferroptosis was coined in the last decade to describe the form of cell death induced by the small molecule erastin. As a specific inducer of ferroptosis, erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into the cytoplasm of cystine, a precursor of glutathione (GSH) in exchange with glutamate and the consequent malfunction of GPX4. Ferroptosis is also promoted by intracellular iron overload and by the iron-dependent accumulation of polyunsaturated fatty acids (PUFA)-derived lipid peroxides. Since depletion of GSH, inactivation of GPX4, altered iron metabolism, and upregulation of PUFA peroxidation by reactive oxygen species are peculiar signs of COVID-19, there is the possibility that SARS-CoV-2 may trigger ferroptosis in the cells of multiple organs, thus contributing to multiorgan damage. Here, we review the molecular mechanisms of ferroptosis and its possible relationship with SARS-CoV-2 infection and multiorgan damage. Finally, we analyze the potential interventions that may combat ferroptosis and, therefore, reduce multiorgan damage.

scholarly journals Mitochondrial regulation of ferroptosis

2021 ◽  
Vol 220 (9) ◽  
Author(s):  
Boyi Gan
Keyword(s):  
Cell Death ◽  
Cell Biology ◽  
Lipid Peroxides ◽  
Disease Treatment ◽  
Mitochondrial Regulation ◽  
Defense Systems ◽  
Regulated Cell Death ◽  
Mitochondrial Lipid ◽  
Mitochondria Functions ◽  
New Evidence

Ferroptosis is a form of iron-dependent regulated cell death driven by uncontrolled lipid peroxidation. Mitochondria are double-membrane organelles that have essential roles in energy production, cellular metabolism, and cell death regulation. However, their role in ferroptosis has been unclear and somewhat controversial. In this Perspective, I summarize the diverse metabolic processes in mitochondria that actively drive ferroptosis, discuss recently discovered mitochondria-localized defense systems that detoxify mitochondrial lipid peroxides and protect against ferroptosis, present new evidence for the roles of mitochondria in regulating ferroptosis, and outline outstanding questions on this fascinating topic for future investigations. An in-depth understanding of mitochondria functions in ferroptosis will have important implications for both fundamental cell biology and disease treatment.

scholarly journals Inactivation of Carbonyl-Detoxifying Enzymes by H2O2 Is a Trigger to Increase Carbonyl Load for Initiating Programmed Cell Death in Plants

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 141 ◽  
Author(s):  
Md. Sanaullah Biswas ◽  
Ryota Terada ◽  
Jun’ichi Mano
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Degradation Products ◽  
Lethal Dose ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Lipid Peroxides ◽  
Carbonyl Reductase ◽  
Sublethal Dose ◽  
20S Proteasome ◽  
Reactive Carbonyl Species

H2O2-induced programmed cell death (PCD) of tobacco Bright Yellow-2 (BY-2) cells is mediated by reactive carbonyl species (RCS), degradation products of lipid peroxides, which activate caspase-3-like protease (C3LP). Here, we investigated the mechanism of RCS accumulation in the H2O2-induced PCD of BY-2 cells. The following biochemical changes were observed in 10-min response to a lethal dose (1.0 mM) of H2O2, but they did not occur in a sublethal dose (0.5 mM) of H2O2. (1) The C3LP activity was increased twofold. (2) The intracellular levels of RCS, i.e., 4-hydroxy-(E)-hexenal and 4-hydroxy-(E)-nonenal (HNE), were increased 1.2–1.5-fold. (3) The activity of a reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent carbonyl reductase, scavenging HNE, and n-hexanal was decreased. Specifically, these are the earliest events leading to PCD. The proteasome inhibitor MG132 suppressed the H2O2-induced PCD, indicating that the C3LP activity of the β1 subunit of the 20S proteasome was responsible for PCD. The addition of H2O2 to cell-free protein extract inactivated the carbonyl reductase. Taken together, these results suggest a PCD-triggering mechanism in which H2O2 first inactivates a carbonyl reductase(s), allowing RCS levels to rise, and eventually leads to the activation of the C3LP activity of 20S proteasome. The carbonyl reductase thus acts as an ROS sensor for triggering PCD.

scholarly journals Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Yi Luo ◽  
Xu Gao ◽  
Luetao Zou ◽  
Miao Lei ◽  
Junming Feng ◽  
...  
Keyword(s):  
Cell Death ◽  
Glutathione Depletion ◽  
Ros Generation ◽  
Mitochondrial Morphology ◽  
Iron Level ◽  
Intracellular Iron ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Regulated Cell Death

Ferroptosis is a new form of regulated cell death, which is mediated by intracellular iron. Although it is reported that bavachin has antitumour effects on several tumour cells and prompts the reactive oxygen species (ROS) generation, it is unclear whether ferroptosis can be induced by bavachin in osteosarcoma (OS) cells. In this study, we found that bavachin inhibits the viability of MG63 and HOS OS cell lines along with an increase in the ferrous iron level, ROS accumulation, malondialdehyde overexpression, and glutathione depletion. Moreover, iron chelators (deferoxamine), antioxidants (Vit E), and ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) reverse bavachin-induced cell death. Bavachin also altered the mitochondrial morphology of OS cells, leading to smaller mitochondria, higher density of the mitochondrial membrane, and reduced mitochondrial cristae. Further investigation showed that bavachin upregulated the expression of transferrin receptor, divalent metal transporter-1, and P53, along with downregulating the expression of ferritin light chain, ferritin heavy chain, p-STAT3 (705), SLC7A11, and glutathione peroxidase-4 in OS cells. More importantly, STAT3 overexpression, SLC7A11 overexpression, and pretreatment with pifithrin-α (P53 inhibitor) rescued OS cell ferroptosis induced by bavachin. The results show that bavachin induces ferroptosis via the STAT3/P53/SLC7A11 axis in OS cells.

scholarly journals Molecular Control of Bacterial Death and Lysis

2008 ◽  
Vol 72 (1) ◽  
pp. 85-109 ◽  
Author(s):  
Kelly C. Rice ◽  
Kenneth W. Bayles
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Exciting Field ◽  
Molecular Control ◽  
Bacterial Physiology ◽  
Regulatory Systems ◽  
Regulated Cell Death ◽  
Bacterial Cell Death ◽  
Contemporary Study ◽  
Biofilm Development

SUMMARY Although the phenomenon of bacterial cell death and lysis has been studied for over 100 years, the contribution of these important processes to bacterial physiology and development has only recently been recognized. Contemporary study of cell death and lysis in a number of different bacteria has revealed that these processes, once thought of as being passive and unregulated, are actually governed by highly complex regulatory systems. An emerging paradigm in this field suggests that, analogous to programmed cell death in eukaryotes, regulated cell death and lysis in bacteria play an important role in both developmental processes, such as competence and biofilm development, and the elimination of damaged cells, such as those irreversibly injured by environmental or antibiotic stress. Further study in this exciting field of bacterial research may provide new insight into the potential evolutionary link between control of cell death in bacteria and programmed cell death (apoptosis) in eukaryotes.

scholarly journals ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Eunhee Park ◽  
Su Wol Chung
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Peroxidation ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Transferrin Receptor ◽  
Receptor Regulation ◽  
Oxygen Species ◽  
Wild Type ◽  
Intracellular Iron ◽  
Transferrin Receptor 1

Abstract Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. Recently, the induction of autophagy has been suggested during ferroptosis. However, this relationship between autophagy and ferroptosis is still controversial and the autophagy-inducing mediator remains unknown. In this study, we confirmed that autophagy is indeed induced by the ferroptosis inducer erastin. Furthermore, we show that autophagy leads to iron-dependent ferroptosis by degradation of ferritin and induction of transferrin receptor 1 (TfR1) expression, using wild-type and autophagy-deficient cells, BECN1+/− and LC3B−/−. Consistently, autophagy deficiency caused depletion of intracellular iron and reduced lipid peroxidation, resulting in cell survival during erastin-induced ferroptosis. We further identified that autophagy was triggered by erastin-induced reactive oxygen species (ROS) in ferroptosis. These data provide evidence that ROS-induced autophagy is a key regulator of ferritin degradation and TfR1 expression during ferroptosis. Our study thus contributes toward our understanding of the ferroptotic processes and also helps resolve some of the controversies associated with this phenomenon.

scholarly journals Benefits of Iron Chelators in the Treatment of Parkinson’s Disease

2021 ◽  
Vol 46 (5) ◽  
pp. 1239-1251
Author(s):  
Xiaoyan Zeng ◽  
Hedi An ◽  
Fei Yu ◽  
Kai Wang ◽  
Lanlan Zheng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Iron Chelator ◽  
Expression Level ◽  
Intracellular Iron ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Regulated Cell Death

AbstractAs a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson’s disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.

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