p53 in ferroptosis regulation: the new weapon for the old guardian

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(5), P. 895 - 910

Published: Jan. 27, 2022

Language: Английский

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GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(3), P. 188890 - 188890

Published: March 29, 2023

Language: Английский

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Exosomes from young healthy human plasma promote functional recovery from intracerebral hemorrhage via counteracting ferroptotic injury

Bioactive Materials, Journal Year: 2023, Volume and Issue: 27, P. 1 - 14

Published: March 23, 2023

Intracerebral hemorrhage (ICH), as a type of life-threatening and highly disabled disease, has limited therapeutic approaches. Here, we show that exosomes derived from young healthy human plasma exhibiting typical features could facilitate functional recovery ICH mice. When these are intraventricularly delivered into the brain after ICH, they mainly distribute around hematoma be internalized by neuronal cells. Strikingly, administration markedly enhanced behavioral mice through reducing injury cell ferroptosis. MiRNA sequencing revealed microRNA-25-3p (miR-25-3p) was differentially expressed miRNA in plasma, compared with old control. Importantly, miR-25-3p mimicked treatment effect on improvement, mediated neuroprotective against ferroptosis ICH. Furthermore, luciferase assay western blotting data illustrated P53 assumed role downstream effector miR-25-3p, thereby regulating SLC7A11/GPX4 pathway to counteract Taken together, findings firstly reveal improve counteracting ferroptotic P53/SLC7A11/GPX4 axis Given easy availability exosomes, our study provides potent strategy for patients quick clinical translation near future.

Language: Английский

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Ferroptosis: a new hunter of hepatocellular carcinoma

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

Published: March 13, 2024

Abstract Ferroptosis is an iron ion-dependent, regulatory cell death modality driven by intracellular lipid peroxidation that plays a key role in the development of HCC. Studies have shown various clinical agents (e.g., sorafenib) ferroptosis inducer-like effects and can exert therapeutic modulating different factors pathway. This implies targeting tumor may be very promising strategy for therapy. In this paper, we summarize prerequisites defense systems occurrence targets drug-mediated action HCC, differences connections between other programmed deaths. We aim to theoretical basis, classical inducers research progress HCC cells, clued treatment regulating network. Further investigation specific mechanisms hepatocellular carcinoma interventions at stages will help us deepen our understanding carcinoma, with view providing new more precise preventive as well measures patients.

Language: Английский

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Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 298 - 298

Published: Feb. 28, 2024

Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, ischemia–reperfusion injuries. linked iron accumulation, eliciting dysfunction antioxidant systems, which favor the production lipid peroxides, membrane damage, ultimately, death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against excess and/or lipid-derived ROS. Here, we discuss interaction between metabolic particular focus on transcription factors implicated in regulation ferroptosis, either as triggers peroxidation or defense pathways.

Language: Английский

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m6A Demethylase FTO-Mediated Upregulation of BAP1 Induces Neuronal Ferroptosis via the p53/SLC7A11 Axis in the MPP⁺/MPTP-Induced Parkinson’s Disease Model

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the involvement of ferroptosis in its pathological mechanism. In this study, effects and mechanism BRCA1-associated protein 1 (BAP1) on neuronal PD were evaluated. Methods: A mouse model was constructed injecting mice with MPTP. Nissl staining, immunohistochemistry, immunofluorescence, Prussian blue staining evaluated histopathology iron distribution. The cell subjecting SK-N-SH cells to MPP+. m6A level BAP1 assessed MeRIP. mRNA levels BAP1, FTO, IGF2BP1, METTL3, YTHDF2, SLC7A11 utilizing RT-qPCR. Protein SLC7A11, p53 measured Western blot. Cell viability using CCK-8 assay, TUNEL used for assessing apoptosis. MDA, GSH, SOD, Fe2+ also measured. interactions among molecules verified RIP dual luciferase reporter ChIP assay. Results: treated MPP+ showed decrease overall BAP1. FTO facilitated demethylation leading an increased expression m6A-binding protein, YTHDF2 recognized decayed methylated reduced stability. FTO/BAP1 axis promoted MPP+-induced suppressing SLC7A11. collaboration p53, Knocking down mitigated MPTP model. Conclusion: m6A-mediated modification regulates cooperating Thus, may be potential therapeutic target treatment.

Language: Английский

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STAT3-mediated ferroptosis is involved in ulcerative colitis

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 188, P. 375 - 385

Published: June 29, 2022

Language: Английский

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p53 Promotes Ferroptosis in Macrophages Treated with Fe₃O₄ Nanoparticles

ACS Applied Materials & Interfaces, Journal Year: 2022, Volume and Issue: 14(38), P. 42791 - 42803

Published: Sept. 16, 2022

Fe3O4 nanoparticles are the most widely used magnetic in biomedicine field. The biodistribution of vivo is determined by capture macrophages; however, effects on macrophages remain poorly understood. Here, we demonstrated that could reduce macrophage viability after 48 h treatment and induce a shift polarization toward M1 phenotype; RNA sequencing revealed activation ferroptosis pathway p53 upregulation compared to control group. expression p53, xCT, glutathione peroxidase 4 (GPX4), transferrin receptor (TFR) was similar erastin-induced macrophages, ultrastructural morphology mitochondria consistent with erastin-treated cells. We DCFH-DA estimate intracellular reactive oxygen species content treated Ana-1 JC-1 fluorescent probes detect mitochondrial membrane potential change; both showed be time-dependent. Fer-1 inhibited reduction glutathione/oxidized (GSH/GSSG) ratio oxidative stress states; therefore, induced macrophages. Finally, pifithrin-α hydrobromide (PFT) as inhibitor verify whether high involved mediating this process. After PFT treatment, live/dead cell rate, TFR, expression, GPX4 consumption were mitigated GSH/GSSG well. This indicates may contribute nanoparticle-induced provide theoretical basis for molecular mechanisms biotoxicity nanoparticles.

Language: Английский

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Ginsenoside Rh3 induces pyroptosis and ferroptosis through the Stat3/p53/NRF2 axis in colorectal cancer cells

Acta Biochimica et Biophysica Sinica, Journal Year: 2023, Volume and Issue: 55(4), P. 587 - 600

Published: April 1, 2023

Ginsenoside Rh3 (GRh3) is a seminatural product obtained by chemical processing after isolation from Chinese herbal medicine that has strong antitumor activity against human tumors. However, its role remains to be elucidated. The aim of this study explore the mechanisms underlying tumor suppressive GRh3 perspective pyroptosis and ferroptosis. eliminates colorectal cancer (CRC) cells activating gasdermin D (GSDMD)-dependent suppressing solute carrier family 7 member 11 (SLC7A11), resulting in ferroptosis activation through Stat3/p53/NRF2 axis. suppresses nuclear factor erythroid 2-related 2 (NRF2) entry into nucleus, leading decrease heme oxygenase 1 (HO-1) expression, which turn promotes NOD-like receptor thermal protein domain associated 3 (NLRP3) caspase-1 expression. Finally, activates GSDMD-dependent pyroptosis. Furthermore, prevents NRF2 entering SLC7A11, causing depletion glutathione (GSH) accumulation iron, lipid reactive oxygen species (ROS) malondialdehyde (MDA), eventually CRC cells. In addition, effectively inhibits proliferation vitro nude mouse models. Collectively, triggers pyroptotic cell death ferroptotic via axis with minimal harm normal cells, showing great anticancer potential.

Language: Английский

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High‑throughput screening identification of a small‑molecule compound that induces ferroptosis and attenuates the invasion and migration of hepatocellular carcinoma cells by targeting the STAT3/GPX4 axis

International Journal of Oncology, Journal Year: 2023, Volume and Issue: 62(3)

Published: Feb. 21, 2023

Hepatocellular carcinoma (HCC) is a lethal malignancy. Although considerable efforts have been made in recent years regarding treatments, effective therapeutic drugs for HCC remain insufficient. In the present study, polyphyllin VI was identified as potential drug by screening natural herbal compounds. The effects of were assessed using Cell Counting Kit‑8, lactate dehydrogenase release and colony formation assays. occurrence ferroptosis determined assessing lipid peroxidation reactive oxygen species, malondialdehyde levels, intracellular ferrous iron mRNA protein levels glutathione peroxidase 4 (GPX4). migratory invasive abilities cells examined wound healing Transwell results revealed that inhibited proliferation, invasion metastasis (HCCLM3 Huh7 cells) inducing ferroptosis. addition, through network pharmacology‑based approach molecular docking analyses, it found may target signal transducer activator transcription 3 (STAT3). treated with or STAT3 inhibitor (Stattic), both which exerted similar inhibitory on expression. Furthermore, immunofluorescence staining significantly nuclear translocation p‑STAT3 cells. Mechanistically, overexpression STAT3, confirmed binds to GPX4 promotes its expression transcription, whereas induces inhibiting STAT3/GPX4 axis. Subsequently, vivo experiments growth subcutaneously transplanted tumors. On whole, findings study suggest inhibits phosphorylation, cells, eventually their metastasis. These data be candidate prevention treatment HCC.

Language: Английский

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