Manganese overexposure results in ferroptosis through the HIF-1α/p53/SLC7A11 pathway in ICR mouse brain and PC12 cells DOI Creative Commons
Jian Chen,

Zehua Tao,

Xinyu Zhang

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 279, P. 116481 - 116481

Published: May 23, 2024

Manganese (Mn) overexposure has been associated with the development of neurological damage reminiscent Parkinson's disease, while underlying mechanisms have yet to be fully characterized. This study aimed investigate leading injury in dopaminergic neurons induced by Mn and identify novel treatment approaches. In vivo vitro models, ICR mice neuron-like PC12 cells were exposed Mn, respectively. We treated them anti-ferroptotic agents ferrostatin-1 (Fer-1), deferoxamine (DFO), HIF-1α activator dimethyloxalylglycine (DMOG) inhibitor LW6. also used p53-siRNA verify mechanism Mn-induced neurotoxicity. Fe concentrations increased brains overexposed Mn. Additionally, Mn-exposed exhibited movement impairment encephalic pathological changes, decreased HIF-1α, SLC7A11, GPX4 proteins p53 protein levels. Fer-1 protective effects against both behavioral biochemical changes. Consistently, vitro, exposure caused ferroptosis-related changes levels, all ameliorated Fer-1. Upregulation DMOG alleviated Mn-associated ferroptosis, LW6 exacerbated neurotoxicity through downregulating HIF-1α. knock-down rescued ferroptosis without altering expression. resulted neurons, mediated HIF-1α/p53/SLC7A11 pathway.

Language: Английский

The diversified role of mitochondria in ferroptosis in cancer DOI Creative Commons
Yue Liu,

Shi-Ping Lu,

Lei‐Lei Wu

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(8)

Published: Aug. 14, 2023

Abstract Ferroptosis is a form of regulated cell death induced by iron-dependent lipid peroxidation, and it has been studied extensively since its discovery in 2012. Induced iron overload ROS accumulation, ferroptosis modulated various cellular metabolic signaling pathways. The GSH-GPX4 pathway, the FSP1-CoQ10 GCH1-BH4 DHODH-CoQH2 system sex hormones suppress ferroptosis. Mitochondrial metabolism regulates mitochondria also undergo morphological change during ferroptosis, these changes include increased membrane density reduced mitochondrial cristae. Moreover, energy oxidative phosphorylation ATP production rates lead to decrease glycolysis rate. In addition, excessive stress induces irreversible damage mitochondria, diminishing organelle integrity. production, potential, fusion fission, mitophagy function Notably, some inhibitors target mitochondria. major mechanism for associated with progression cancer. Metastasis-prone or metastatic cancer cells are more susceptible Inducing tumor shows very promising potential treating drug-resistant cancers. this review, we present brief retrospect characteristics then discuss regulation highlight unique role played cells. Furthermore, explain how functions as double-edged sword well novel therapies aimed at selectively manipulating eradication.

Language: Английский

Citations

154
Ferroptosis Nanomedicine: Clinical Challenges and Opportunities for Modulating Tumor Metabolic and Immunological Landscape DOI
Huocheng Yang,

Xuemei Yao,

Yingqi Liu

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(16), P. 15328 - 15353

Published: Aug. 13, 2023

Ferroptosis, a type of regulated cell death driven by iron-dependent phospholipid peroxidation, has captured much attention in the field nanomedicine since it was coined 2012. Compared with other modes such as apoptosis and pyroptosis, ferroptosis many distinct features molecular mechanisms cellular morphology, representing promising strategy for treating cancers that are resistant to conventional therapeutic modalities. Moreover, recent insights collectively reveal is tightly connected maintenance tumor immune microenvironment (TIME), suggesting potential application therapies evoking robust antitumor immunity. From biochemical perspective, intricately multiple metabolic pathways, including iron metabolism, lipid redox etc., highlighting importance elucidate relationship between metabolism developing therapies. In this review, we provide comprehensive discussion on current understanding ferroptosis-inducing thoroughly discuss various traits tumors, which offer opportunities direct inhibition through nanointegrated approach. Extending from complex impact TIME, also discussed those important considerations development ferroptosis-based immunotherapy, challenges strategies enhance ferroptosis-enabled immunostimulatory effects while avoiding side effects. We envision study may facilitate translation nanomedicines treatment.

Language: Английский

Citations

52
Mn-based cGAS-STING activation for tumor therapy DOI Open Access
Aiping Huang, Wenhu Zhou

Chinese Journal of Cancer Research, Journal Year: 2023, Volume and Issue: 35(1), P. 19 - 43

Published: Jan. 1, 2023

Immunotherapy has efficiently revolutionized the treatment of human neoplastic diseases. However, overall responsive rate current immunotherapy is still unsatisfactory, benefiting only a small proportion patients. Therefore, significant attention been paid to modulation tumor microenvironment (TME) for enhancement immunotherapy. Interestingly, recent studies have shown that cyclic GMP-AMP synthase-stimulator interferon gene (cGAS-STING) was initially found as an innate immune sensor recognize cytoplasmic DNA (such bacterial, viral, micronuclei, and mitochondrial). It promising signaling pathway activate antitumor responses via type I production. Notably, Mn2+ be critical molecule sensitize activation cGAS-STING better This led development Mn2+-based strategies pathway. In this review, we aimed summarize progress field, focusing on following three aspects. First, briefly introduced activation, its regulation effect immunity cycle discussed. Along with this, several agonists were their potential immunotherapeutic drugs. Then, basic biological functions illustrated, roles in activation. Next, systematically reviewed immunotherapy, which can classified by methods based alone or combined other therapeutic modalities. We finally speculated future perspectives field provided rational suggestions develop therapeutics.

Language: Английский

Citations

48
Crosstalk between ferroptosis and cuproptosis: From mechanism to potential clinical application DOI Open Access
Na Liu,

Min‐Bin Chen

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116115 - 116115

Published: Jan. 5, 2024

Ferroptosis and cuproptosis, regulated forms of cell death resulting from metal ion accumulation, are closely related in terms occurrence, metabolism, signaling pathways, drug resistance. Notably, it is now understood that these processes play crucial roles regulating physiological pathological processes, especially tumor development. Consequently, ferroptosis cuproptosis have gained increasing significance as potential targets for anti-cancer This article systematically outlines the molecular mechanisms cross-talk components both elucidating their impacts on cancer. Furthermore, investigates clinical perspective targeted cancer chemotherapy, immunotherapy, radiotherapy. Our discussion extends to a comparative analysis nanoparticles developed based cancer, contrasting them with current conventional therapies. Opportunities challenges treatment explored, emphasizing therapeutic direction co-targeting cuproptosis. The also attempts analyze applications this approach while summarizing existing barriers require overcoming.

Language: Английский

Citations

45
Ferroptosis: Mechanisms and role in diabetes mellitus and its complications DOI
Pan Liu, Zhengdong Zhang, Yichen Cai

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102201 - 102201

Published: Jan. 19, 2024

Language: Английский

Citations

44
STING promotes ferroptosis through NCOA4-dependent ferritinophagy in acute kidney injury DOI Creative Commons

Lini Jin,

Binfeng Yu,

Hongju Wang

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 208, P. 348 - 360

Published: Aug. 26, 2023

Ferroptosis in tubules has been implicated the pathogenesis of acute kidney injury (AKI), whereas regulatory mechanism remains unclear. The stimulator interferon genes (STING) is previously recognized as a critical mediator innate immunity via DNA-sensing pathway and increasingly linked to lipid peroxidation, hallmark ferroptosis. Herein we investigated role underlying STING AKI models established by ischemia/reperfusion (IR) C57BL mice. expression level was predominantly increased after IR treatment. Besides, deficiency markedly alleviated IR-induced tissue damage renal dysfunction. Consistently, vitro experiments demonstrated that increase ferroptotic cell death, ROS production decrease GSH peroxidase 4 (GPX4) tubular cells subjected ferroptosis agonist or hypoxia/reoxygenation intervention were all mitigated genetic pharmacological inhibition STING, while exacerbated overexpression. Further, these detrimental effects overexpression relied on induction ferritinophagy, i.e. autophagic degradation ferritin, leading iron overload. Mechanistically, mediated initiation ferritinophagy through interacting with nuclear receptor coactivator (NCOA4), fundamental for transfer ferritin into lysosome. Collectively, contributes during ischemic facilitating NCOA4-mediated shows potential promising therapeutic choice AKI.

Language: Английский

Citations

43
Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases DOI Creative Commons
Leilei Chen, Qingqing Shen, Yingjuan Liu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 2, 2025

Language: Английский

Citations

8
Amino acid metabolism disorder and oxidative stress took part in EGCG alleviating Mn-caused ferroptosis via miR-9-5p/got1 axis DOI
Qin Zhou,

Zhiyu Hao,

Ming-Yue Qiu

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 489, P. 137656 - 137656

Published: Feb. 21, 2025

Language: Английский

Citations

4
Nanoparticle‐Mediated STING Activation for Cancer Immunotherapy DOI

Yongjuan Li,

Xinyan Li,

Jinmeng Yi

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(19)

Published: March 11, 2023

Abstract As the first line of host defense against pathogenic infections, innate immunity plays a key role in antitumor immunotherapy. The cyclic GMP‐AMP synthase (cGAS)‐stimulator interferon genes (STING) (cGAS‐STING) pathway has attracted much attention because secretion various proinflammatory cytokines and chemokines. Many STING agonists have been identified applied into preclinical or clinical trials for cancer However, fast excretion, low bioavailability, nonspecificity, adverse effects small molecule limit their therapeutic efficacy vivo application. Nanodelivery systems with appropriate size, charge, surface modification are capable addressing these dilemmas. In this review, mechanism cGAS‐STING is discussed agonists, focusing on nanoparticle‐mediated therapy combined cancers, summarized. Finally, future direction challenges nano‐STING expounded, emphasizing pivotal scientific problems technical bottlenecks hoping to provide general guidance its

Language: Английский

Citations

34
Manganese-Enriched Zinc Peroxide Functional Nanoparticles for Potentiating Cancer Immunotherapy DOI
Mengli Zhou, Shuang Liang, Dan Liu

et al.

Nano Letters, Journal Year: 2023, Volume and Issue: 23(22), P. 10350 - 10359

Published: Nov. 6, 2023

Immunotherapies have shown high clinical success, however, the therapeutical efficacy is largely restrained by insufficient immune activation and an immunosuppressive microenvironment. Herein, we report tumor microenvironment (TME)-responsive manganese-enriched zinc peroxide nanoparticles (MONPs) for synergistic cancer immunotherapy inducing immunogenic death (ICD) of cells activating stimulator interferon gene (STING) pathway. MONPs especially disassociate upon exposure to acidic tissue in situ generate •OH ICD effect. Moreover, Mn2+ activated STING synergistically induced secretion type I inflammatory cytokines specific T cell responses. Meanwhile, relieved immunosuppression TME through decreasing Tregs polarizing M2 macrophages M1 unleash a cascade adaptive response. In combination with anti-PD-1 antibody, showed superior inhibiting growth preventing lung metastasis. Our study demonstrates feasibility functional amplify innate stimulation, showing prominent strategy immunotherapy.

Language: Английский

Citations

33