T-2 Toxin Induces Cardiotoxicity by Activating Ferroptosis and Inhibiting Heme Oxygenase-1 DOI
Chi Wang, Li Zhang, Jun He

et al.

Published: Jan. 1, 2023

T-2 toxin, a natural secondary sesquiterpenoid metabolite produced by numerous strains of Fusarium fungi, is prevalent in both contaminated food and the environment. toxin known to be highly toxic cardiovascular system, but precise mechanisms that lead toxin-induced cardiotoxicity are not yet fully comprehended. Recent findings indicate ferroptosis pivotal factor damage exhibits strong correlation with detrimental impacts toxin. The present study was designed examine involvement cardiac injury. Male mice human cardiomyocytes were subjected for 24 h induce acute vivo vitro studies, respectively. Our results demonstrated increased reactive oxygen species production, malondialdehyde, decreased glutathione/oxidized glutathione adenosine triphosphate levels. Furthermore, observed activate ferroptosis, as evidenced an increase iron (Fe2+) concentration upregulation prostaglandin endoperoxide synthase 2, downregulation peroxidase 4 ferritin heavy chain, well ferroptotic morphological alterations. Inhibition Liproxstatin-1 reversed Additionally, heme oxgenase-1 (HO-1) expression exacerbates oxidative damage, which can further aggravated HO-1 inhibition Sn-protoporphyrin. These provide novel insights into mechanism suggest targeting may represent promising cardioprotective strategy against

Language: Английский

Regulated cell death in myocardial ischemia–reperfusion injury DOI
Q. Xiang, Xin Yi,

Xue‐Hai Zhu

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 35(3), P. 219 - 234

Published: Nov. 17, 2023

Language: Английский

Citations

132
Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases DOI Creative Commons
Yumin Wang, Jing Hu, Shuang Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

Citations

77
The Mechanisms of Ferroptosis Under Hypoxia DOI Creative Commons
Xīn Gào, Wei Hu, Dianlun Qian

et al.

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(7), P. 3329 - 3341

Published: July 17, 2023

Abstract Ferroptosis is a new form of programmed cell death, which characterized by the iron-dependent accumulation lipid peroxidation and increase ROS, resulting in oxidative stress death. Iron, lipid, multiple signaling pathways precisely control occurrence implementation ferroptosis. The mainly include Nrf2/HO-1 pathway, p62/Keap1/Nrf2 pathway. Activating pathway inhibits promotes Furthermore, some factors also participate ferroptosis under hypoxia, such as HIF-1, NCOA4, DMT1. Meanwhile, related with hypoxia-related diseases, MIRI, cancers, AKI. Accordingly, appears to be therapeutic target for diseases.

Language: Английский

Citations

58
New Insights into the Role of Ferroptosis in Cardiovascular Diseases DOI Creative Commons
Anna Maria Fratta Pasini,

Chiara Stranieri,

Fabiana Busti

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(6), P. 867 - 867

Published: March 10, 2023

Cardiovascular diseases (CVDs) are the principal cause of disease burden and death worldwide. Ferroptosis is a new form regulated cell mainly characterized by altered iron metabolism, increased polyunsaturated fatty acid peroxidation reactive oxygen species, depletion glutathione inactivation peroxidase 4. Recently, series studies have indicated that ferroptosis involved in cardiac vascular cells has key impact on mechanisms leading to CVDs such as ischemic heart disease, ischemia/reperfusion injury, cardiomyopathies, failure. In this article, we reviewed molecular mechanism current understanding pathophysiological role some cardiomyopathies. Moreover, comprehension machinery governing cardiomyocytes may provide insights into preventive therapeutic strategies CVDs.

Language: Английский

Citations

32
Inflammation, dysregulated iron metabolism, and cardiovascular disease DOI Creative Commons
Shaina L. Rosenblum

Frontiers in Aging, Journal Year: 2023, Volume and Issue: 4

Published: Feb. 3, 2023

Iron is an essential trace element associated with both pathologic deficiency and toxic overload. Thus, systemic cell iron metabolism are highly controlled processes regulated by protein expression localization, as well turnover, through the action of cytokines status. in heart challenging because overload cardiac disease. Also cardiovascular disease inflammation, many diseases caused or include inflammatory component. In addition, inflammation closely linked. Hepcidin, master regulator metabolism, induced cytokine IL-6 such among acute phase proteins secreted liver part response. state, homeostasis dysregulated, commonly resulting hypoferremia, low serum iron. Less characterized general, even less known about how impacts handling. This review highlights what respect to heart. Expression metabolism-related uptake efflux these types outlined. Evidence for strong co-morbid relationship between also reviewed. Known connections discussed goal linking this tissue, a connection that has been relatively under-appreciated component function state. Therapeutic options connecting balance emphasized, main being bring attention alterations system.

Language: Английский

Citations

23
The molecular mechanisms and potential drug targets of ferroptosis in myocardial ischemia–reperfusion injury DOI Creative Commons
Chen-Hua Zhang, Yujie Yan, Qi Luo

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 340, P. 122439 - 122439

Published: Jan. 24, 2024

Myocardial ischemia–reperfusion injury (MIRI), caused by the initial interruption and subsequent restoration of coronary artery blood, results in further damage to cardiac function, affecting prognosis patients with acute myocardial infarction. Ferroptosis is an iron-dependent, superoxide-driven, non-apoptotic form regulated cell death that involved pathogenesis MIRI. characterized accumulation lipid peroxides (LOOH) redox disequilibrium. Free iron ions can induce oxidative stress as a substrate Fenton reaction lipoxygenase (LOX) participate inactivation variety antioxidants including CoQ10 GPX4, destroying balance causing death. The metabolism amino acid, iron, lipids, associated pathways, considered specific hallmark ferroptosis. This review systematically summarizes latest research progress on mechanisms ferroptosis discusses analyzes therapeutic approaches targeting alleviate

Language: Английский

Citations

13
Iron metabolism and ferroptosis in health and diseases: the crucial role of mitochondria in meta-bolically active tissues DOI Creative Commons
Angela Catapano, Fabiano Cimmino, Lidia Petrella

et al.

The Journal of Nutritional Biochemistry, Journal Year: 2025, Volume and Issue: unknown, P. 109888 - 109888

Published: March 1, 2025

Iron is essential in various physiological processes, but its accumulation leads to oxidative stress and cell damage, thus iron homeostasis has be tightly regulated. Ferroptosis an iron-dependent non-apoptotic regulated death characterized by overload ROS accumulation. Mitochondria are organelles playing a crucial role metabolism involved ferroptosis. MitoNEET, protein of mitochondrial outer membrane, key element this process. Ferroptosis, altering levels several metabolically active organs, linked non-communicable diseases. For example, the liver hepatic fibrosis cirrhosis, accelerating NAFLD progression, muscle cells contributes damage leading sarcopenia, brain associated neurodegeneration. The aim review investigate intricate balance regulation focusing on mitochondria stress, analyzing ferroptosis implications health disease.

Language: Английский

Citations

1
Ferroptosis—A New Dawn in the Treatment of Organ Ischemia–Reperfusion Injury DOI Creative Commons
Linxiang Zhou, Shangting Han, Jiayu Guo

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(22), P. 3653 - 3653

Published: Nov. 17, 2022

Ischemia–reperfusion (I/R) is a common pathological phenomenon that occurs in numerous organs and diseases. It generally results from secondary damage caused by the recovery of blood flow reoxygenation, followed ischemia organ tissues, which often accompanied severe cellular death. Currently, effective treatments for I/R injury (IRI) are limited. Ferroptosis, new type regulated cell death (RCD), characterized iron overload iron-dependent lipid peroxidation. Mounting evidence has indicated close relationship between ferroptosis IRI. Ferroptosis plays significantly detrimental role progression IRI, targeting may be promising approach treatment Considering substantial progress made study this review, we summarize mechanisms therapeutic targets

Language: Английский

Citations

34
Targeting ferroptosis as a promising therapeutic strategy to treat cardiomyopathy DOI Creative Commons
Huiyan Sun, Dandan Chen,

Wenjing Xin

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: April 13, 2023

Cardiomyopathies are a clinically heterogeneous group of cardiac diseases characterized by heart muscle damage, resulting in myocardium disorders, diminished function, failure, and even sudden death. The molecular mechanisms underlying the damage to cardiomyocytes remain unclear. Emerging studies have demonstrated that ferroptosis, an iron-dependent non-apoptotic regulated form cell death iron dyshomeostasis lipid peroxidation, contributes development ischemic cardiomyopathy, diabetic doxorubicin-induced septic cardiomyopathy. Numerous compounds exerted potential therapeutic effects on cardiomyopathies inhibiting ferroptosis. In this review, we summarize core mechanism which ferroptosis leads these cardiomyopathies. We emphasize emerging types can inhibit delineate their beneficial treating This review suggests pharmacologically may be strategy for cardiomyopathy treatment.

Language: Английский

Citations

17
Ferrostatin-1 Blunts Right Ventricular Hypertrophy and Dysfunction in Pulmonary Arterial Hypertension by Suppressing the HMOX1/GSH Signaling DOI

Jiawei Song,

Yihang Chen,

Yufei Chen

et al.

Journal of Cardiovascular Translational Research, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 21, 2023

Language: Английский

Citations

15