Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(11)

Published: Nov. 26, 2024

Abstract Regulated cell death (RCD) refers to the form of that can be regulated by various biomacromolecules. Each modalities have their distinct morphological changes and molecular mechanisms. However, intense evidences suggest lipid peroxidation common feature initiates propagates death. Excessive alters property membrane further damage proteins nucleic acids, which is implicated in human pathologies. Here, we firstly review classical chain process peroxidation, clarify current understanding myriad roles mechanisms RCD types. We also discuss how involves diseases such intimate association between peroxidation-driven leveraged develop rational therapeutic strategies.

Language: Английский

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Iron chelators loaded on myocardiocyte mitochondria-targeted nanozyme system for treating myocardial ischemia-reperfusion injury in mouse models

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 15, 2025

Ferroptosis plays a critical role in myocardial ischemia-reperfusion injury (MIRI), posing significant clinical challenge. Nanoenzymes like cerium oxide (CeO2) hold promise for mitigating oxidative damage and inhibiting ferroptosis, but their delivery efficiency biological activity require optimization. This study aims to develop targeted nanozyme system MIRI treatment by integrating CeO2 with mesoporous polydopamine (mPDA) dexrazoxane (DXZ) achieve synergistic therapeutic effects. A biomineralization technique was used synthesize nanoparticles (2–3 nm) within mPDA, forming ~ 130 nm composite (Ce@mPDA). Surface modifications cardiac homing peptide (CHP) triphenylphosphine (TPP) enabled hierarchical targeting injured myocardium mitochondria. DXZ-loaded Ce@mPDA-C/P (D/Ce@mPDA-C/P) were evaluated vitro mouse model effects on stress, apoptosis, inflammation, function. D/Ce@mPDA-C/P exhibited robust ROS scavenging, sustained DXZ release, efficient mitochondrial targeting. The significantly reduced upregulated GPX4 expression, inhibited modulated the inflammatory microenvironment. Long-term studies demonstrated reductions fibrosis improvements function, including enhanced fractional shortening ejection fraction. effectively combines antioxidant properties of iron-chelating DXZ, providing promising strategy MIRI. approach may expand use advance nanomedicine-based interventions repair.

Language: Английский

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The role of ferroptosis in liver injury after cold ischemia–reperfusion in rats with autologous orthotopic liver transplantation

Journal of Artificial Organs, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Using autologous orthotopic liver transplantation (AOLT) model in rats, the effect of lipid reactive oxygen species (L-ROS) inhibitor Ferrostain-1 on ferroptosis signal pathway was observed to determine whether occurred rat injury after cold ischemia-reperfusion (I/R). Thirty-two healthy adult SPF male SD 8 ~ 10 weeks old, weight 240 260 g, were divided into four groups by method random number table (n = 8): sham group, I/R + Fer-1 DFO group. In ferristatin-1(5 mg /kg) intraperitoneally injected 30 min before surgery; 100 mg/kg 1 h operation and 12 operation. Blood samples taken from inferior hepatic vena cava 24 reperfusion. After anesthesia, rats killed part their tissue removed. The pathological changes sections under a high-power microscope, evaluated. Serum malondialdehyde (MDA) serum levels ALT, AST IL-6 determined ELISA method, Reduced glutathione (GSH), peroxidase 4 (GPX4), MDA, Fe2 superoxide dismutase (SOD) tissue. Compared with IL-6,MDA, ALT group obviously higher (P < 0.05); MDA Fe

Language: Английский

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Based on bioinformatics, SESN2 negatively regulates ferroptosis induced by ischemia reperfusion via the System Xc−/GPX4 pathway

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 29, 2025

Introduction Cerebral ischemia–reperfusion (IR) causes severe secondary brain injury. Previous studies have demonstrated that ferroptosis is involved in IR-induced However, whether IR induces microvascular endothelial cells (BMVECs) not fully understood. Materials and methods Oxygen–glucose deprivation/reoxygenation (OGDR) was performed bEND.3 to mimic injury vitro , a focal cerebral model created C57BL/6 mice. Transcriptomic sequencing of the first, followed by bioinformatics analysis. Differentially expressed gene (DEG) enrichment analysis highlighted ferroptosis-related pathways. Results Using Venn analysis, nine DEGs were identified, namely, Slc3a2 Slc7a11 Ccn2 Tfrc Atf3 Chac1 Gch1 Lcn2 Sesn2 . Protein–protein interaction (PPI) combined with molecular complex detection (MCODE) identified six hub genes, Ddit3 Trib3 Ppp1r15a Gadd45a Spearman’s correlation revealed significant between genes DEGs. After reperfusion, levels indicators elevated, expression proteins Xc− GPX4 decreased. SESN2 key antioxidant regulator. silencing reduced System GPX4, whereas overexpression promoted GPX4. Discussion These results suggest negative regulator ferroptosis. Enhancing can alleviate through activation Xc−/GPX4 pathway. By integrating mechanistic exploration, this study plays crucial role BMVECs injury, acting as via

Language: Английский

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TREM2 protects against LPS-induced murine acute lung injury through suppressing macrophage ferroptosis

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114247 - 114247

Published: Feb. 12, 2025

Language: Английский

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Involvement of Oxidative Stress and Antioxidants in Modification of Cardiac Dysfunction Due to Ischemia–Reperfusion Injury

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 340 - 340

Published: March 14, 2025

Delayed reperfusion of the ischemic heart (I/R) is known to impair recovery cardiac function and produce a wide variety myocardial defects, including ultrastructural damage, metabolic alterations, subcellular Ca2+-handling abnormalities, activation proteases, changes in gene expression. Although I/R injury has been reported induce formation reactive oxygen species (ROS), inflammation, intracellular Ca2+ overload, generation oxidative stress considered play critical role development dysfunction. Increases production superoxide, hydroxyl radicals, oxidants, such as hydrogen peroxide hypochlorous acid, occur hearts subjected injury. In fact, mitochondria are major source excessive ROS due impairment electron transport system well xanthine oxidase NADPH oxidase. Nitric oxide synthase, mainly present endothelium, also activated injury, leading nitric oxide, which, upon combination with superoxide generates nitrosative stress. Alterations function, sarcolemma, sarcoplasmic reticulum activities, mitochondrial phosphorylation, protease simulated exposing oxyradical-generating (xanthine plus oxidase) or H2O2. On other hand, endogenous antioxidants dismutase, catalase, glutathione peroxidase, concentration transcription factor (Nrf2), which modulates expression various antioxidants, depressed hearts. Furthermore, pretreatment catalase N-acetylcysteine, mercaptopropionylglycerine observed attenuate I/R-induced handling Ca2+-regulatory activities; additionally, it found depress improve function. These observations indicate that intimately involved pathological effects different alterations Thus, we faced task developing safe effective agents for upregulating therapy

Language: Английский

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Electroacupuncture Attenuates Cerebral Ischemia–Reperfusion Injury by Inhibiting Ferroptosis via the p53/SLC7A11 Pathway

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2025, Volume and Issue: 52(5)

Published: April 9, 2025

ABSTRACT Acupuncture has demonstrated efficacy in treating post‐stroke complications. Electroacupuncture (EA) ameliorates neurological outcomes cerebral ischemia models, yet its mechanisms remain unclear. This study investigated EA's role reducing ischemia–reperfusion injury (CIRI) a rat model, focusing on ferroptosis. A CIRI model was established via the MCAO/R method. Rats were randomly assigned to five experimental groups: Sham, MCAO/R, + COTI‐2, EA and COTI‐2 EA. We evaluated function with Zausinger scoring. 2,3,5‐Triphenyltetrazolium chloride (TTC) staining assessed infarct size, while haematoxylin–eosin (HE) examined neuronal damage. Transmission electron microscopy analysed mitochondrial changes associated ferroptosis, Perl measured iron levels neurons. The biomarkers including glutathione (GSH), reactive oxygen species (ROS) malondialdehyde (MDA), measured. expression of p53 , SLC7A11 GPX4 by qRT‐PCR Western blot. enhanced function, reduced alleviated excessive serum accumulation, increased antioxidant markers (GSH, GPX4) decreased lipid peroxidation (ROS, MDA), attenuating peroxidation. Additionally, it reversed morphological blot analyses revealed that downregulated upregulating expression. In summary, ferroptosis activated after CIRI, ameliorated deficits models modulating p53/SLC7A11 axis counteract oxidative stress‐induced ultimately providing neuroprotective benefits.

Language: Английский

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Extracellular vesicles containing GAS6 protect the liver from ischemia-reperfusion injury by enhancing macrophage efferocytosis via MerTK-ERK-COX2 signaling

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Sept. 10, 2024

Language: Английский

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Extracellular Vesicles Containing GAS6 Protect the Liver from Ischemia-Reperfusion Injury by Enhancing Macrophage Efferocytosis via MerTK-ERK-COX2 Signaling

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

Hepatic ischaemia-reperfusion injury (HIRI) is a significant issue during liver transplantation and surgery, contributing to the failure or even mortality. Although extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown substantial potentials in cell replacement therapy of various organ IRIs, precise mechanisms remain unclear. In this study, we demonstrate that systemic MSC-EVs administration predominantly absorbed by macrophages, verified it could significantly reduce inflammatory response mice suffered HIRI. Furthermore, treatment with induces macrophage polarization toward an anti-inflammatory phenotype. Mechanistically, proteomic profiling reveals enrichment growth arrest-specific 6 (GAS6) MSC-EVs, promoting activation myeloid-epithelial-reproductive tyrosine kinase/extracellular regulated protein kinases/cyclooxygenase 2 (MerTK/ERK/COX2) signaling pathway macrophages further enhancing their efferocytosis efficiency. Knockdown GAS6 via lentiviral transfection inhibition MerTK using UNC2025 partially eliminates protective effects on injury. Overall, our findings support enriched execute anti-inflammation effect, highlighting bases modulation function as promising approach IRI.

Language: Английский

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The Role of Ferroptosis in Liver Injury after Cold Ischemia-Reperfusion in Rats with Autologous Orthotopic Liver Transplantation

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Using autologous orthotopic liver transplantation（AOLT） model in rats, the effect of lipid reactive oxygen species（L-ROS） inhibitor Ferrostain-1 on ferroptosis signal pathway was observed to determine whether occurred rat injury after cold Cold ischemia-reperfusion(I/R). Thirty-two healthy adult SPF male SD rats，8 ~ 10 weeks old, weight 240 260g, It is divided into four groups by method random number table(n = 8)：Sham group,I/R group,I/R+Fer-1 group,I/R+DFO group. In I/R+Fer-1 group, Intraperitoneal injection ferristatin-1(5mg /kg) 30 minutes before surgery；In I/R+DFO DFO 100mg/kg injected intraperitoneally 1 h operation and 12 operation. Blood samples were taken from inferior hepatic vena cava 24 hours reperfusion, After anesthesia, rats killed part their tissue removed. The pathological changes sections under high power microscope, evaluated；Determination serum malondialdehyde (MDA) levels ALT, AST, IL-6 ELISA method，Determination reduced glutathione (GSH), peroxidase 4 (GPX4), MDA, Fe2+ superoxide dismutase (SOD) tissue. Compared with Sham IL-6,MDA, AST ALT I/R group obviously higher (P < 0.05)；The MDA Fe²⁺ significantly increased (P < SOD, GSH GPX4 decreased. IL-6, lower than those at reperfusion；In level decreased significantly, while intestinal 0.05)；In SOD 0.05).Ferroptosis involved pathophysiological process ischemia-reperfusion AOLT rats.

Language: Английский

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