Nrf2/UBE3B protects against acute lung injury by inhibiting ferritinophagy through the ubiquitination of NCOA4 DOI Creative Commons
Yanjun Wang, Hui Dong, Yunfan Gu

et al.

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

Published: Oct. 14, 2024

Abstract Iron overload and ferroptosis are associated with intestinal ischemia reperfusion (II/R)-induced acute lung injury (ALI). However, the mechanisms underlying regulation of iron homeostasis remain unclear. Nrf2 regulates cellular homeostasis; however, its impact on ALI pathology mechanism action requires further investigation. Ubiquitin ligase E3B (UBE3B) plays a critical role in proteasome pathway, which is essential for protein turnover ubiquitin-mediated signaling. A recent study found that UBE3B oxidative stress; it remains unknown whether related to Nrf2. Furthermore, exact largely uncharacterized. In present study, immunohistochemical analysis expression type II alveolar epithelial cells (AECII) was conducted be increased II/R-ALI. Western blot indicated hyperactivation may alleviate stress, thereby protecting against ALI. Moreover, involved metabolism dysfunction ferroptosis. deficiency enhanced process nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy ferrous ion content, whereas overexpression reversed harmful effects knockdown AECⅡ, promote AECⅡ This highlights Nrf2/UBE3B/NCOA4 axis II/R-ALI pathogenesis, suggesting activation promising strategy treatment.

Language: Английский

Nuclear receptor coactive 4-mediated ferritinophagy: a key role of heavy metals toxicity DOI

Wan-Xue Xu,

Wen Xue, Yupeng Fu

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Language: Английский

Citations

2
18beta-glycyrrhetinic acid alleviates deoxynivalenol-induced hepatotoxicity by inhibiting GPX4-dependent ferroptosis DOI

Chenchen Song,

Wei Wang,

Yu Hua

et al.

Toxicon, Journal Year: 2025, Volume and Issue: unknown, P. 108228 - 108228

Published: Jan. 1, 2025

Language: Английский

Citations

1
Ferritinophagy: multifaceted roles and potential therapeutic strategies in liver diseases DOI Creative Commons

Kejia Wu,

Wei Zhao,

Zeyu Hou

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 25, 2025

Ferritinophagy, the selective autophagic degradation of ferritin to release iron, is emerging as a critical regulator iron homeostasis and key player in pathogenesis various liver diseases. This review comprehensively examines mechanisms, regulation, multifaceted roles ferritinophagy health disease. Ferritinophagy intricately regulated by several factors, including Nuclear Receptor Coactivator 4 (NCOA4), Iron regulatory proteins signaling pathways such mTOR AMPK. These mechanisms ensure proper utilization prevent overload, which can induce oxidative stress ferroptosis. In diseases, exhibits dual roles. fibrosis, promoting hepatic stellate cells (HSCs) cell senescence reduce fibrosis progression. However, non-alcoholic fatty disease (NAFLD), chronic may exacerbate injury through overload stress. hepatocellular carcinoma (HCC), be harnessed novel therapeutic strategy inducing ferroptosis cancer cells. Additionally, implicated drug-induced sepsis-associated damage, highlighting its broad impact on pathology. also explores crosstalk between other autophagy pathways, mitophagy lipophagy, collectively influence cellular Understanding these interactions essential for developing comprehensive strategies targeting multiple pathways. summary, complex dynamic process with significant implications provides an in-depth analysis ferritinophagy's potential target, emphasizing need further research elucidate role

Language: Английский

Citations

1
Zearalenone induces liver injury in mice through ferroptosis pathway DOI

Lige Bao,

Yongze Huang,

Fuhua Gu

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 952, P. 175875 - 175875

Published: Aug. 30, 2024

Language: Английский

Citations

7
Hesperidin Alleviates Hepatic Injury Caused by Deoxynivalenol Exposure through Activation of mTOR and AKT/GSK3β/TFEB Pathways DOI

Xin Wang,

Hao Chen, Junze Jiang

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(25), P. 14349 - 14363

Published: June 13, 2024

Deoxynivalenol (DON) is a common agricultural mycotoxin that chemically stable and not easily removed from cereal foods. When organisms consume food made contaminated crops, it can be hazardous to their health. Numerous studies in recent years have found hesperidin (HDN) has hepatoprotective effects on wide range of toxins. However, few scholars explored the potential HDN attenuating DON-induced liver injury. In this study, we established low-dose DON exposure model intervened with three doses HDN, acting male C57 BL/6 mice AML12 cells, which served as vivo vitro models, respectively, investigate protective mechanism against exposure-induced The results suggested disrupted hepatic autophagic fluxes, thereby impairing structure function, significantly attenuated these changes. Further revealed alleviated excessive autophagy through mTOR pathway lysosomal dysfunction AKT/GSK3β/TFEB pathway. Overall, our study could ameliorate flux disorders via pathway, reducing

Language: Английский

Citations

6
Naringenin alleviates liver fibrosis by triggering autophagy-dependent ferroptosis in hepatic stellate cells DOI Creative Commons
Ting Yu,

Xuejia Lu,

Liang Yan

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28865 - e28865

Published: March 29, 2024

Inhibition of activated hepatic stellate cells (HSCs) is a promising approach for treating liver fibrosis, and the ferroptosis has emerged as pivotal mechanism to achieve this inhibition. The effects naringenin, flavonoid with anti-inflammatory properties, have not been thoroughly examined in fibrosis. Therefore, we used cholestasis model study effect naringenin on Our findings demonstrated significant exacerbation tissue damage fibrosis mice subjected bile duct ligation (BDL), accompanied by substantial upregulation fibrogenesis-related gene expression. Notably, administration markedly alleviated injury these mice. Furthermore, exhibited inhibitory activation HSCs, concurrently inducing ferroptosis. Importantly, significantly increased autophagic activity HSCs. This was counteracted co-administration autophagy inhibitor 3-MA, leading notable reduction naringenin-induced HSC In BDL mice, mitigating suggesting potential correlation These results provide novel insights into molecular mechanisms highlight autophagy-dependent therapeutic strategy

Language: Английский

Citations

5
Cu2O nanoparticles with morphology-dependent peroxidase mimic activity: a novel colorimetric biosensor for deoxynivalenol detection DOI
Xiaodong Zhu,

BoBo Zhang,

Junhao Wang

et al.

Microchimica Acta, Journal Year: 2024, Volume and Issue: 191(10)

Published: Sept. 10, 2024

Language: Английский

Citations

5
Targeting Ferroptosis and Ferritinophagy Improves Tooth Extraction Socket Healing in Type 2 Diabetes Mellitus Via Human Bone Marrow Mesenchymal Stem Cells Modulation DOI
Yifeng Bian, Jianfeng Li, Fan Xu

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Disorders of Iron Metabolism: A “Sharp Edge” of Deoxynivalenol-Induced Hepatotoxicity DOI Creative Commons
Haoyue Guan,

Yujing Cui,

Zichun Hua

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 165 - 165

Published: March 1, 2025

Background/Objectives: Deoxynivalenol (DON), known as vomitoxin, is one of the most common mycotoxins produced by Fusarium graminearum, with high detection rates in feed worldwide. Ferroptosis a novel mode cell death characterized lipid peroxidation and accumulation reactive oxygen species. Although it has been demonstrated that DON can induce ferroptosis liver, specific mechanisms pathways are still unknown. The aim this experiment was to investigate iron metabolism disorders livers mice, thereby triggering causing toxic damage liver. Methods: Male C57 mice were treated at 5 mg/kg BW concentration an vivo model. After sampling, organ coefficient monitoring, liver function test, histopathological analysis, Fe2+ content oxidative stress-related indexes performed. mRNA protein expression Nrf2 its downstream genes also detected using series methods including quantitative real-time PCR, immunofluorescence double-labeling, Western blotting analysis. Results: cause mouse. Specifically, we found mouse group exhibited pathological necrosis, inflammatory infiltration, cytoplasmic vacuolization, elevated relative weight, significant changes indexes. Meanwhile, substantial reduction levels glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) indicated caused stress Notably, exposure increased Malondialdehyde (MDA) which provides strong evidence for occurrence disorders. Most importantly, Nrf2, important pathway ferroptosis, along genes, heme oxygenase (HO-1), quinone oxidoreductase (NQO1), peroxidase (GPX4), solute carrier gene (SLC7a11), significantly inhibited group. Conclusions: Based on our results, closely associated DON-induced livers, suggesting maintaining hepatic homeostasis activating may be potential target mitigating hepatotoxicity future.

Language: Английский

Citations

0
The Therapeutic Potential of Autophagy-Dependent Ferroptosis in Hepatocellular Carcinoma DOI

琪 蒋

World Journal of Cancer Research, Journal Year: 2025, Volume and Issue: 15(03), P. 99 - 107

Published: Jan. 1, 2025

Language: Английский

Citations

0