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.

scholarly journals The role of reactive oxygen species and nitric oxide in programmed cell death associated with self-incompatibility

2015 ◽  
Vol 66 (10) ◽  
pp. 2869-2876 ◽  
Author(s):  
Irene Serrano ◽  
María C. Romero-Puertas ◽  
Luisa M. Sandalio ◽  
Adela Olmedilla
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Self Incompatibility

scholarly journals Ferroptosis in plants: triggers, proposed mechanisms, and the role of iron in modulating cell death

2020 ◽  
Author(s):  
Ayelén Mariana Distéfano ◽  
Gabriel Alejandro López ◽  
Nicolás Setzes ◽  
Fernanda Marchetti ◽  
Maximiliano Cainzos ◽  
...  
Keyword(s):  
Cell Death ◽  
Metabolic Pathways ◽  
Oxygen Species ◽  
Cell Death Pathway ◽  
Plant Life ◽  
Regulated Cell Death ◽  
Dependent Cell ◽  
Plant Life Cycle ◽  
High Degree

Abstract Regulated cell death plays key roles during essential processes throughout the plant life cycle. It takes part in specific developmental programs and maintains homeostasis of the organism in response to unfavorable environments. Ferroptosis is a recently discovered iron-dependent cell death pathway characterized by the accumulation of lipid reactive oxygen species. In plants, ferroptosis shares all the main hallmarks described in other systems. Those specific features include biochemical and morphological signatures that seem to be conserved among species. However, plant cells have specific metabolic pathways and a high degree of metabolic compartmentalization. Together with their particular morphology, these features add more complexity to the plant ferroptosis pathway. In this review, we summarize the most recent advances in elucidating the roles of ferroptosis in plants, focusing on specific triggers, the main players, and underlying pathways.

scholarly journals The Role of NADPH Oxidase 1–Derived Reactive Oxygen Species in Paraquat-Mediated Dopaminergic Cell Death

2009 ◽  
Vol 11 (9) ◽  
pp. 2105-2118 ◽  
Author(s):  
Ana Clara Cristóvão ◽  
Dong-Hee Choi ◽  
Graça Baltazar ◽  
M. Flint Beal ◽  
Yoon-Seong Kim
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Dopaminergic Cell ◽  
Nadph Oxidase 1

scholarly journals Mitochondria-Ros Crosstalk in the Control of Cell Death and Aging

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Saverio Marchi ◽  
Carlotta Giorgi ◽  
Jan M. Suski ◽  
Chiara Agnoletto ◽  
Angela Bononi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Redox State ◽  
Balance Of Power ◽  
Molecular Pathways ◽  
Oxygen Species ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway ◽  
Induce Cell Death

Reactive oxygen species (ROS) are highly reactive molecules, mainly generated inside mitochondria that can oxidize DNA, proteins, and lipids. At physiological levels, ROS function as “redox messengers” in intracellular signalling and regulation, whereas excess ROS induce cell death by promoting the intrinsic apoptotic pathway. Recent work has pointed to a further role of ROS in activation of autophagy and their importance in the regulation of aging. This review will focus on mitochondria as producers and targets of ROS and will summarize different proteins that modulate the redox state of the cell. Moreover, the involvement of ROS and mitochondria in different molecular pathways controlling lifespan will be reported, pointing out the role of ROS as a “balance of power,” directing the cell towards life or death.

scholarly journals Functional inactivation of the oestrogen receptor by the antioestrogen, ZM 182780, sensitises tumour cells to reactive oxygen species

1999 ◽  
Vol 161 (2) ◽  
pp. 199-210 ◽  
Author(s):  
CJ Newton ◽  
N Drummond ◽  
CH Burgoyne ◽  
V Speirs ◽  
GK Stalla ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Oestrogen Receptor ◽  
Reactive Oxygen ◽  
Mitochondrial Activity ◽  
Oxygen Species ◽  
Rat Pituitary ◽  
Functional Inactivation ◽  
Mediate Cell

Reactive oxygen species (ROS) play a fundamental role in both apoptotic and necrotic cell death. Their importance is highlighted by studies showing that they mediate cell death in response to radiotherapy and to some forms of chemotherapy. Here we provide the first evidence for a role of ROS in response to an antiendocrine agent currently undergoing clinical trials. Using the oestrogen receptor (ER) containing rat pituitary GH3 cell line, we show that cell death is induced by the pure steroidal antioestrogen, ZM 182780, and that this is blocked by the antioxidant, N-acetyl cysteine (NAC). By flow cytometry, we show that, prior to the onset of DNA breakdown measured by ELISA, ZM 182780 exposure has no significant effect on intracellular oxidant concentrations. In contrast, ZM 182780 exposure greatly increases sensitivity to oxidants generated by blocking cellular antioxidant pathways and from exogenous administration of hydrogen peroxide (H2O2). As both necrosis and apoptosis are controlled by mitochondrial function, further experiments conducted to determine mitochondrial membrane potential (Delta|gWm) have indicated that the ZM 182780-induced loss of ER function increases the ease with which oxidants collapse mitochondrial activity and, as a consequence, cell death.

Role of reactive oxygen species-mediated mitochondrial dysregulation in 3-bromopyruvate induced cell death in hepatoma cells

2008 ◽  
Vol 40 (6) ◽  
pp. 607-618 ◽  
Author(s):  
Ji Su Kim ◽  
Keun Jae Ahn ◽  
Jeong-Ah Kim ◽  
Hye Mi Kim ◽  
Jong Doo Lee ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Hepatoma Cells ◽  
Oxygen Species

scholarly journals Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Mariachiara Buccarelli ◽  
Quintino Giorgio D’Alessandris ◽  
Paola Matarrese ◽  
Cristiana Mollinari ◽  
Michele Signore ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Strong Increase ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species

Abstract Background Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, characterized by a poor prognosis mainly due to recurrence and therapeutic resistance. It has been widely demonstrated that glioblastoma stem-like cells (GSCs), a subpopulation of tumor cells endowed with stem-like properties is responsible for tumor maintenance and progression. Moreover, it has been demonstrated that GSCs contribute to GBM-associated neovascularization processes, through different mechanisms including the transdifferentiation into GSC-derived endothelial cells (GdECs). Methods In order to identify druggable cancer-related pathways in GBM, we assessed the effect of a selection of 349 compounds on both GSCs and GdECs and we selected elesclomol (STA-4783) as the most effective agent in inducing cell death on both GSC and GdEC lines tested. Results Elesclomol has been already described to be a potent oxidative stress inducer. In depth investigation of the molecular mechanisms underlying GSC and GdEC response to elesclomol, confirmed that this compound induces a strong increase in mitochondrial reactive oxygen species (ROS) in both GSCs and GdECs ultimately leading to a non-apoptotic copper-dependent cell death. Moreover, combined in vitro treatment with elesclomol and the alkylating agent temozolomide (TMZ) enhanced the cytotoxicity compared to TMZ alone. Finally, we used our experimental model of mouse brain xenografts to test the combination of elesclomol and TMZ and confirmed their efficacy in vivo. Conclusions Our results support further evaluation of therapeutics targeting oxidative stress such as elesclomol with the aim of satisfying the high unmet medical need in the management of GBM.

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