Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression DOI Creative Commons
Yu Cui, Zhaolong Zhang, Xin Zhou

et al.

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: Oct. 30, 2021

Many neurological diseases involve neuroinflammation, during which overproduction of cytokines by immune cells, especially microglia, can aggregate neuronal death. Ferroptosis is a recently discovered cell metabolism-related form death and RSL3 well-known inducer ferroptosis. Here, we aimed to investigate the effects in neuroinflammation sensitivity different type microglia macrophage ferroptosis.Here, used quantitative RT-PCR analysis ELISA analyze production proinflammatory cytokine macrophages after lipopolysaccharides (LPS) stimulation. We CCK8, LDH, flow cytometry evaluate RSL3-induced Western blot was test activation inflammatory signaling pathway knockdown efficiency. SiRNA-mediated interference conducted GPX4 or Nrf2 BV2 microglia. Intraperitoneal injection LPS performed systemic inflammation severity vivo conditions.We found that ferroptosis inhibited (LPS)-induced peritoneal (PMs) ferroptosis-independent manner, whereas ferroptosis-conditioned medium significantly triggered PMs. Different showed varied Mechanistically, induced protein expression inhibit RNA Polymerase II recruitment transcription start site genes repress transcription, protect cells from Furthermore, simultaneously Fer-1 ameliorated LPS-induced conditions.These data revealed role macrophages, identified as novel inhibitor inflammation, uncovered molecular regulation Thus, targeting using should consider both pro-ferroptosis effect anti-inflammation achieve optimal outcome.

Language: Английский

Ferroptosis: mechanisms, biology and role in disease DOI
Xuejun Jiang, Brent R. Stockwell, Marcus Conrad

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(4), P. 266 - 282

Published: Jan. 25, 2021

Language: Английский

Citations

4434
Ferroptosis, a new form of cell death: opportunities and challenges in cancer DOI Creative Commons

Yanhua Mou,

Jun Wang, Jinchun Wu

et al.

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: March 29, 2019

Ferroptosis is a novel type of cell death with distinct properties and recognizing functions involved in physical conditions or various diseases including cancers. The fast-growing studies ferroptosis cancer have boosted perspective for its usage therapeutics. Here, we review the current findings regulation especially focus on function ncRNAs mediating process ferroptotic how was relation to other regulated deaths. Aberrant diverse types tissues were summarized, elaborated recent data about actors some "conventional" drugs natural compounds as inducers cancer. Finally, deliberate future orientation cells unsettled issues, which may forward speed clinical use induction treatment.

Language: Английский

Citations

1455
Role of GPX4 in ferroptosis and its pharmacological implication DOI

Tobias Seibt,

Bettina Proneth, Marcus Conrad

et al.

Free Radical Biology and Medicine, Journal Year: 2018, Volume and Issue: 133, P. 144 - 152

Published: Sept. 13, 2018

Language: Английский

Citations

1134
The Metabolic Underpinnings of Ferroptosis DOI Creative Commons
Jiashuo Zheng, Marcus Conrad

Cell Metabolism, Journal Year: 2020, Volume and Issue: 32(6), P. 920 - 937

Published: Nov. 20, 2020

Language: Английский

Citations

957
The chemical basis of ferroptosis DOI
Marcus Conrad, Derek A. Pratt

Nature Chemical Biology, Journal Year: 2019, Volume and Issue: 15(12), P. 1137 - 1147

Published: Nov. 18, 2019

Language: Английский

Citations

730
Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion DOI Creative Commons
Li Yang,

Dongcheng Feng,

Zhanyu Wang

et al.

Cell Death and Differentiation, Journal Year: 2019, Volume and Issue: 26(11), P. 2284 - 2299

Published: Feb. 8, 2019

Ferroptosis is a recently identified form of regulated cell death defined by the iron-dependent accumulation lipid reactive oxygen species. has been studied in various diseases such as cancer, Parkinson's disease, and stroke. However, exact function mechanism ferroptosis ischemia/reperfusion (I/R) injury, especially intestine, remains unknown. Considering unique conditions required for ferroptosis, we hypothesize that ischemia promotes immediately after intestinal reperfusion. In contrast to conventional strategies employed I/R studies, focused on ischemic phase. Here verified assessing proferroptotic changes along with protein peroxidation levels during The inhibition liproxstatin-1 ameliorated I/R-induced injury. Acyl-CoA synthetase long-chain family member 4 (ACSL4), which key enzyme regulates composition, shown contribute execution but its role needs clarification. present study, used rosiglitazone (ROSI) siRNA inhibit ischemia/hypoxia-induced ACSL4 vivo vitro. results demonstrated before reperfusion protected against death. Further investigation revealed special 1 (Sp1) was crucial transcription factor increased binding promoter region. Collectively, this study demonstrates closely associated critical lethal process. Sp1 an important promoting expression. These suggest effective mechanistic approach injury prevention treatment.

Language: Английский

Citations

717
The emerging role of ferroptosis in inflammation DOI Open Access

Yitian Sun,

Peng Chen,

Bingtao Zhai

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2020, Volume and Issue: 127, P. 110108 - 110108

Published: March 29, 2020

Ferroptosis is a newly discovered type of cell death triggered by intracellular phospholipid peroxidation that morphologically, biologically and genetically distinct from other types death. classified as regulated necrosis more immunogenic than apoptosis. To date, compelling evidence indicates ferroptosis plays an important role in inflammation, several antioxidants functioning inhibitors have been shown to exert anti-inflammatory effects experimental models certain diseases. Our review provides overview the link between inflammation; better understanding mechanisms underlying inflammation may hasten development promising therapeutic strategies involving address inflammation.

Language: Английский

Citations

578
Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases DOI Creative Commons
Yi Yu, Yan Yuan,

Fanglin Niu

et al.

Cell Death Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: July 26, 2021

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

Language: Английский

Citations

460
Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death DOI Creative Commons

Anna Martina Battaglia,

Roberta Chirillo, Ilenia Aversa

et al.

Cells, Journal Year: 2020, Volume and Issue: 9(6), P. 1505 - 1505

Published: June 20, 2020

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

Language: Английский

Citations

418
Ferroptosis in cancer and cancer immunotherapy DOI Creative Commons
Lei Zhao, Xiaoxue Zhou, Feng Xie

et al.

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(2), P. 88 - 116

Published: Feb. 1, 2022

Abstract The hallmark of tumorigenesis is the successful circumvention cell death regulation for achieving unlimited replication and immortality. Ferroptosis a newly identified type dependent on lipid peroxidation which differs from classical programmed in terms morphology, physiology biochemistry. broad spectrum injury tumor tolerance are main reasons radiotherapy chemotherapy failure. effective rate immunotherapy as new treatment method less than 30%. can be seen radiotherapy, chemotherapy, immunotherapy; therefore, ferroptosis activation may potential strategy to overcome drug resistance mechanism traditional cancer treatments. In this review, characteristics causes by briefly described. addition, three metabolic regulations its crosstalk with signaling pathways summarized. Collectively, these findings suggest vital role based interaction immunotherapy, thus, indicating remarkable treatment.

Language: Английский

Citations

415