Hydrogen sulfide alleviates particulate matter-induced emphysema and airway inflammation by suppressing ferroptosis

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 186, P. 1 - 16

Published: April 29, 2022

Redox imbalance is an vital mechanism for COPD. At present, insufficient researches have been conducted on the protective effect of hydrogen sulfide (H2S) PM-induced However, whether H2S exerts anti-injury role by blocking ferroptosis and restoring redox equilibrium remain to be investigated. Human lung tissue samples were collected IHC staining, expressions Nrf2, ferritinophagy- ferroptosis-related proteins observed. The WT C57BL/6 Nrf2 knockout mice models established with PM(200 μg per mouse). NaHS(Exogenous H2S) was injected intraperitoneally 30 min in advance. Twenty-nine days later, tissues evaluated HE's PERLS-DAB's staining. Meanwhile, inflammation oxidative stress indicators iron levels assessed corresponding ELISA kit. Related protein detected through Western blot. BEAS-2B cells or without exposed PM2.5 36 h. Cell viability, mitochondrial morphology, inflammatory cytokines, antioxidant factors, levels, autophagic flux ROS, LIP MitoROS, MMP, as well related specific methods, respectively. In addition, V5-Nrf2, siRNA, inhibitor ML385, PPAR-γ GW9662, autophagy CQ, chelator DFO Fer-1 used verify target signaling pathways. We found that COX2, MDA other factors increased, while markers GPX4, GSH GSH-Px significantly decreased, active accumulation COPD patients, PM-exposured Nrf2-KO PM2.5-mediated cell models. NaHS pretreatment markedly inhibited emphysema airway alleviating ferroptotic changes vivo vitro. With use V5-Nrf2 overexpression plasmid, siRNA pathway inhibitors, we activates PPAR-γ, inhibites ferritinophagy makers LC3B, NCOA4 FTH1 cells. Moreover, anti-ferroptotic further verified activation signal MEF This research suggested alleviated via balance inhibiting regulating Nrf2-PPAR-ferritinophagy pathway.

Language: Английский

---

FUNDC1 insufficiency sensitizes high fat diet intake-induced cardiac remodeling and contractile anomaly through ACSL4-mediated ferroptosis

Metabolism, Journal Year: 2021, Volume and Issue: 122, P. 154840 - 154840

Published: July 29, 2021

Language: Английский

---

HucMSC-derived exosomes delivered BECN1 induces ferroptosis of hepatic stellate cells via regulating the xCT/GPX4 axis

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(4)

Published: April 8, 2022

Abstract Activated hepatic stellate cells (HSCs) are significant in liver fibrosis. Our past investigations have shown that human umbilical cord mesenchymal stem (hucMSCs) and their secreted exosomes (MSC-ex) could alleviate fibrosis via restraining HSCs activation. However, the mechanisms underlying efficacy were not clear. Ferroptosis is a regulatory cell death caused by excessive lipid peroxidation, it plays vital role occurrence development of In present study, we aimed to study proferroptosis effect mechanism MSC-ex HSCs. collected purified from MSCs. Proferroptosis was examined line LX-2 CCl4 induced mice. Gene knockdown or overexpression approaches used investigate biofactors MSC-ex-mediated ferroptosis regulation. Results: trigger promoting ferroptosis-like death, ROS formation, mitochondrial dysfunction, Fe 2 + release, peroxidation LX-2. Glutathione peroxidase 4 (GPX4) crucial regulator ferroptosis. We found intravenous injection significantly decreased glutathione expression activated collagen deposition experimental mouse fibrotic livers. Mechanistically, derived BECN1 promoted suppressing xCT-driven GPX4 expression. addition, ferritinophagy necroptosis might also play MSC-ex-promoted death. Knockdown MSC diminished anti-fibrosis effects may promote xCT/GPX4 mediated through delivery highlights as potential biofactor for alleviating

Language: Английский

---

Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression

Advanced Science, Journal Year: 2023, Volume and Issue: 10(13)

Published: March 23, 2023

Intervertebral disc degeneration (IVDD)-induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress-induced ferroptosis in nucleus pulposus (NP) cells vitro. PDA NPs scavenge reactive oxygen species (ROS), chelate Fe

Language: Английский

---

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Advanced Science, Journal Year: 2023, Volume and Issue: 10(24)

Published: June 21, 2023

Emerging evidence suggests that ferroptosis, a unique regulated cell death modality is morphologically and mechanistically different from other forms of death, plays vital role in the pathophysiological process neurodegenerative diseases, strokes. Accumulating supports ferroptosis as critical factor diseases strokes, pharmacological inhibition therapeutic target for these diseases. In this review article, core mechanisms are overviewed roles strokes described. Finally, emerging findings treating through This demonstrates by bioactive small-molecule compounds (ferroptosis inhibitors) could be effective treatments highlights potential promising avenue used to prevent article will shed light on developing novel regimens slow down progression future.

Language: Английский

---

High Level of Uric Acid Promotes Atherosclerosis by Targeting NRF2-Mediated Autophagy Dysfunction and Ferroptosis

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 21

Published: April 18, 2022

Atherosclerotic vascular disease (ASVD) is the leading cause of death worldwide. Hyperuricemia fourth risk factor for atherosclerosis after hypertension, diabetes, and hyperlipidemia. The mechanism hyperuricemia affecting occurrence development has not been fully elucidated. Mononuclear macrophages play critical roles in all stages atherosclerosis. Studies have confirmed that both ferroptosis promote atherosclerosis, but whether high level uric acid (HUA) promotes by regulating remains unclear. We found HUA significantly promoted atherosclerotic plaque downregulated protein NRF2/SLC7A11/GPX4 signaling pathway ApoE-/- mice. Next, we evaluated effect inhibitor ferrostatin-1 (Fer-1) treatment on formation macrophage-derived foam cells. cells, decreased cell viability, increased iron accumulation lipid peroxidation treated with oxidized low-density lipoprotein (oxLDL); these effects were reversed Fer-1 treatment. Mechanistically, inhibited autophagy pathway. activated upregulated ferroptosis-associated proteins. Moreover, an NRF2 inducer (tertbutyl hydroquinone (TBHQ)) activator (rapamycin (RAPA)) could reverse inhibitory survival. Our results suggest HUA-induced involved plaques. More importantly, enhancing inhibiting activating may alleviate These findings might contribute to a deeper understanding role pathogenesis provide therapeutic target ASVD associated hyperuricemia.

Language: Английский

---

FUNDC1 interacts with GPx4 to govern hepatic ferroptosis and fibrotic injury through a mitophagy-dependent manner

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 55, P. 45 - 60

Published: Feb. 23, 2023

Liver fibrosis is a life-threatening pathological anomaly which usually evolves into advanced liver cirrhosis and hepatocellular carcinoma although limited therapeutic option readily available. FUN14 domain containing 1 (FUNDC1) mitophagy receptor with little information in fibrosis. This study was designed to examine the role for FUNDC1 carbon tetrachloride (CCl4)-induced injury. GEO database analysis subsequent validation of biological processes including western blot, immunofluorescence, co-immunoprecipitation were applied clarify regulatory on ferroptosis. Our data revealed elevated levels tissues patients fibrotic injury CCl4-challenged mice. deletion protected against CCl4-induced hepatic anomalies Moreover, ameliorated ferroptosis vivo vitro. Mechanically, interacted glutathione peroxidase (GPx4), selenoenzyme neutralize lipid hydroperoxides ferroptosis, via its 96–133 amino acid facilitate GPx4 recruitment mitochondria from cytoplasm. entered through mitochondrial protein import system-the translocase outer membrane/translocase inner membrane (TOM/TIM) complex, prior degradation mainly along ROS-induced damaged mitochondria, resulting hepatocyte Taken together, our favored that promoted binding translocation TOM/TIM where degraded by trigger Targeting may be promising approach

Language: Английский

---

Ferroptosis in sepsis: The mechanism, the role and the therapeutic potential

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 5, 2022

Sepsis is a common critical illness in the Intensive care unit(ICU) and its management treatment has always been major challenge medicine. The dysregulated host response to infection, causing systemic multi-organ multi-system damage main pathogenesis. Notably, intense stress during sepsis can lead metabolic disturbances of ions, lipids energy organism. Ferroptosis an iron-dependent, non-apoptotic cell death distinguished by disruption iron metabolism iron-dependent accumulation lipid peroxides. Mounting researches have established that ferroptosis essential part anti-inflammatory sepsis, drugs targeting ferroptosis-related molecules, such as inhibitors, are gradually proving their effectiveness sepsis. This paper summarizes reviews pathogenesis ferroptosis, regulatory network, vital involvement initiation related organ damage, finally discusses possible target provided above mechanisms, describes dilemmas well outlook, hope finding more links between providing new perspectives for future

Language: Английский

---

International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis

Autophagy, Journal Year: 2024, Volume and Issue: 20(6), P. 1213 - 1246

Published: March 6, 2024

Macroautophagy/autophagy is a complex degradation process with dual role in cell death that influenced by the types are involved and stressors they exposed to. Ferroptosis an iron-dependent oxidative form of characterized unrestricted lipid peroxidation context heterogeneous plastic mechanisms. Recent studies have shed light on involvement specific autophagy (e.g. ferritinophagy, lipophagy, clockophagy) initiating or executing ferroptotic through selective anti-injury proteins organelles. Conversely, other forms reticulophagy lysophagy) enhance cellular defense against damage. Dysregulated autophagy-dependent ferroptosis has implications for diverse range pathological conditions. This review aims to present updated definition ferroptosis, discuss influential substrates receptors, outline experimental methods, propose guidelines interpreting results.

Language: Английский

---

Autophagy-Dependent Ferroptosis in Cancer

Antioxidants and Redox Signaling, Journal Year: 2023, Volume and Issue: 39(1-3), P. 79 - 101

Published: Feb. 3, 2023

Significance: Autophagy is a self-degrading process that determines cell fate in response to various environmental stresses. In contrast autophagy-mediated survival, the signals, mechanisms, and effects of autophagy-dependent death remain obscure. The discovery ferroptosis provides paradigm for understanding relationship between aberrant degradation pathways excessive lipid peroxidation driving regulated death. Recent Advances: Ferroptosis was originally described as an autophagy-independent iron-mediated nonapoptotic Current studies reveal level intracellular autophagy positively correlated with sensitivity. Selective autophagic proteins (e.g., ferritin, SLC40A1, ARNTL, GPX4, CDH2) or organelles droplets mitochondria) promotes by inducing iron overload and/or peroxidation. Several upstream autophagosome regulators TMEM164), downstream receptors HPCAL1), danger signals DCN) are selectively required ferroptosis-related autophagy, but not starvation-induced autophagy. induction effective approach eliminate drug-resistant cancer cells. Critical Issues: How different activate modulate sensitivity fully understood. Identifying direct protein effectors ferroptotic remains challenge. Future Directions: Further molecular mechanics immune consequences critical development precision antitumor therapies. Antioxid. Redox Signal. 39, 79-101.

Language: Английский

---