Histone deacetylase 6 deficiency protects the liver against ischemia/reperfusion injury by activating PI3K/AKT/mTOR signaling DOI
Jie Pan, Q C Yu, Yaodong Song

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(4)

Published: Feb. 9, 2024

Abstract Liver transplantation (LT) is the only effective method to treat end‐stage liver disease. Hepatic ischemia‐reperfusion injury (IRI) continues limit prognosis of patients receiving LT. Histone deacetylase 6 (HDAC6) a unique HDAC member involved in inflammation and apoptosis. However, its role mechanism hepatic IRI have not yet been reported. We examined HDAC6 levels tissue from LT patients, mice challenged with IRI, hepatocytes subjected hypoxia/reoxygenation (H/R). In addition, global‐knockout (HDAC6‐KO) mice, adeno‐associated virus‐mediated liver‐specific overexpressing (HDAC6‐LTG) their corresponding controls were used construct models. histology, inflammatory responses, apoptosis detected assess injury. The molecular mechanisms explored vivo vitro. Moreover, HDAC6‐selective inhibitor tubastatin A was detect therapeutic effect on IRI. Together, our results showed that expression significantly upregulated I/R surgery, by (H/R) treatment. Compared control deficiency mitigated inhibiting responses apoptosis, whereas HDAC6‐LTG displayed opposite phenotype. Further experiments show bound deacetylated AKT improved activating PI3K/AKT/mTOR signaling. conclusion, key mediator functions promote via Targeting inhibition may be promising approach attenuate

Language: Английский

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases DOI Creative Commons
Yumin Wang, Jing Hu, Shuang Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

Citations

77
Uridine Alleviates Sepsis-Induced Acute Lung Injury by Inhibiting Ferroptosis of Macrophage DOI Open Access

Kai Lai,

Congkuan Song,

Minglang Gao

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5093 - 5093

Published: March 7, 2023

Uridine metabolism is extensively reported to be involved in combating oxidative stress. Redox-imbalance-mediated ferroptosis plays a pivotal role sepsis-induced acute lung injury (ALI). This study aims explore the of uridine ALI and regulatory mechanism ferroptosis. The Gene Expression Omnibus (GEO) datasets including tissues lipopolysaccharides (LPS) -induced model or human blood sample sepsis were collected. In vivo vitro, LPS was injected into mice administered THP-1 cells generate inflammatory models. We identified that phosphorylase 1 (UPP1) upregulated septic samples significantly alleviated injury, inflammation, tissue iron level lipid peroxidation. Nonetheless, expression biomarkers, SLC7A11, GPX4 HO-1, upregulated, while synthesis gene (ACSL4) greatly restricted by supplementation. Moreover, pretreatment inducer (Erastin Era) weakened inhibitor (Ferrostatin-1 Fer-1) strengthened protective effects uridine. Mechanistically, inhibited macrophage activating Nrf2 signaling pathway. conclusion, dysregulation novel accelerator for supplementation may offer potential avenue ameliorating suppressing

Language: Английский

Citations

57
COVID-19 Causes Ferroptosis and Oxidative Stress in Human Endothelial Cells DOI Creative Commons
Stanislovas S. Jankauskas, Urna Kansakar, Celestino Sardu

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 326 - 326

Published: Jan. 31, 2023

Oxidative stress and endothelial dysfunction have been shown to play crucial roles in the pathophysiology of COVID-19 (coronavirus disease 2019). On these grounds, we sought investigate impact on lipid peroxidation ferroptosis human cells. We hypothesized that oxidative induced by cells could be linked outcome. Thus, collected serum from patients hospital admission, incubated sera with cells, comparing effects generation reactive oxygen species (ROS) between who survived did not survive. found non-survivors significantly increased peroxidation. Moreover, markedly regulated expression levels main markers ferroptosis, including GPX4, SLC7A11, FTH1, SAT1, a response was rescued silencing TNFR1 Taken together, our data indicate survive triggers

Language: Английский

Citations

48
Ferroptosis and Senescence: A Systematic Review DOI Open Access
Donatella Coradduzza, Antonella Congiargiu, Zhichao Chen

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3658 - 3658

Published: Feb. 11, 2023

Senescence is a cellular aging process in all multicellular organisms. It characterized by decay functions and proliferation, resulting increased damage death. This condition plays an essential role the significantly contributes to development of age-related complications. On other hand, ferroptosis systemic cell death pathway excessive iron accumulation followed generation reactive oxygen species (ROS). Oxidative stress common trigger this may be induced various factors such as toxins, drugs, inflammation. Ferroptosis linked numerous disorders, including cardiovascular disease, neurodegeneration, cancer. believed contribute tissue organ occurring with aging. has also been pathologies, diseases, diabetes, In particular, senescent cells have shown produce inflammatory cytokines pro-inflammatory molecules that can these conditions. turn, health known play pathologies promoting damaged or diseased contributing inflammation often associated. Both senescence are complex pathways still not fully understood. Further research needed thoroughly investigate processes identify potential interventions target order prevent treat systematic review aims assess mechanisms underlying link connecting senescence, ferroptosis, aging, whether they exploited block limit physiological elderly people for healthy longevity.

Language: Английский

Citations

45
Crocetin antagonizes parthanatos in ischemic stroke via inhibiting NOX2 and preserving mitochondrial hexokinase-I DOI Creative Commons
Hao Wu, Ying Li, Qian Zhang

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 21, 2023

Abstract Parthanatos is one of the major pathways programmed cell death in ischemic stroke characterized by DNA damage, poly (ADP-ribose) polymerases (PARP) activation, and (PAR) formation. Here we demonstrate that crocetin, a natural potent antioxidant compound from Crocus sativus , antagonizes parthanatos stroke. We reveal mechanistically, crocetin inhibits NADPH oxidase 2 (NOX2) activation to reduce reactive oxygen species (ROS) PAR production at early stage parthanatos. Meanwhile PARylated hexokinase-I (HK-I) novel substrate E3 ligase RNF146 interacts with HK-I suppress RNF146-mediated degradation later parthanatos, preventing mitochondrial dysfunction damage ultimately trigger irreversible death. Our study supports further development as potential drug candidate for and/or treating

Language: Английский

Citations

25
Analysis and identification of oxidative stress-ferroptosis related biomarkers in ischemic stroke DOI Creative Commons

Lin-Ming Zhang,

Xing-ling Liang,

Gui-fei Xiong

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 15, 2024

Abstract Studies have shown that a series of molecular events caused by oxidative stress is associated with ferroptosis and oxidation after ischemic stroke (IS). Differential analysis was performed to identify differentially expressed mRNA (DEmRNAs) between IS control groups. Critical module genes were identified using weighted gene co-expression network (WGCNA). DEmRNAs, critical genes, stress-related (ORGs), ferroptosis-related (FRGs) crossed screen for intersection mRNAs. Candidate mRNAs screened based on the protein–protein interaction (PPI) MCODE plug-in. Biomarkers two types machine learning algorithms, obtained. Functional items related pathways biomarkers set enrichment (GSEA). Finally, single-sample GSEA (ssGSEA) Wilcoxon tests used differential immune cells. An miRNA-mRNA-TF created. Quantitative real-time polymerase chain reaction (qRT-PCR) verify expression levels in There 8287 DE The turquoise selected as IS. Thirty intersecting overlaps. Seventeen candidate also identified. Four (CDKN1A, GPX4, PRDX1, PRDX6) machine-learning algorithms. results indicated steroid biosynthesis. Nine cells (activated B neutrophils) markedly different We 3747 regulatory pairs network, including hsa-miR-4469-CDKN1A-BACH2 hsa-miR-188-3p-GPX4-ATF2. CDKN1A, PRDX6 upregulated samples compared samples. This study suggests four are significantly provides new reference diagnosis treatment

Language: Английский

Citations

12
Ferroptosis in organ ischemia–reperfusion injuries: recent advancements and strategies DOI

Xiaoyu Luan,

Peng Chen, Longyu Miao

et al.

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: March 31, 2024

Language: Английский

Citations

11
Silibinin Attenuates Ferroptosis in Acute Kidney Injury by Targeting FTH1 DOI Creative Commons

Yijian Deng,

Liying Zeng, Huaxi Liu

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 77, P. 103360 - 103360

Published: Sept. 20, 2024

Acute kidney injury (AKI) is primarily caused by renal ischemia-reperfusion (IRI), which one of the most prevalent triggers. Currently, preventive and therapeutic measures remain limited. Ferroptosis plays a significant role in pathophysiological process IRI-induced AKI considered key target for improving its outcomes. Silibinin, polyphenolic flavonoid, possesses diverse pharmacological properties widely used as an effective agent liver diseases. Recent studies have reported that silibinin may improves diseases, though underlying mechanism unclear. In this study, we investigated whether protects against explored action. Our findings indicated pretreatment with alleviated dysfunction, pathological damage, inflammation IRI-AKI mice. Furthermore, results demonstrated inhibited ferroptosis both vivo vitro. Proteome microarrays were to identify silibinin's target, our revealed binds FTH1. This binding affinity was confirmed through molecular docking, SPRi, CETSA, DARTS. Additionally, co-IP assays disrupted NCOA4-FTH1 interaction, inhibiting ferritinophagy. Finally, inhibitory effects on reversed knocking down FTH1 conclusion, study shows effectively alleviates targeting reduce ferroptosis, suggesting could be developed potential managing treating AKI.

Language: Английский

Citations

11
Mifepristone protects acetaminophen induced liver injury through NRF2/GSH/GST mediated ferroptosis suppression DOI
Yanyun Shi,

Nahua Xu,

B Liu

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 222, P. 229 - 243

Published: June 19, 2024

Language: Английский

Citations

9
Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells DOI Creative Commons
Ceyda Colakoglu Bergel, Işıl Ezgi Eryılmaz, Gülşah Çeçener

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 18, 2025

The current study established the first in vitro Encorafenib resistance protocol BRAF-mutated malignant melanoma (MM) cells and investigated resistance-related mechanisms. After establishing Encorafenib-resistant A375-MM cells, resistant-related mechanisms were using WST-1, Annexin V, cell cycle, morphological analysis, live-cell, Western blot, RNA-Seq, transmission electron microscopy-(TEM), oxidative stress iron colorimetric assay. most resistant group, called A375-R, was determined treated with a constant dose of 10 nM over 3 months. viability, apoptosis, G0/G1 arrest reflected acquired chemoresistance. Autophagic Beclin LC3 proteins, AKT signaling increased A375-R. RNA-Seq results also exhibited altered epigenetic regulation resistance; particularly ferritin family members, ion transport pathways. Then, NCOA4, FTH1, levels detected A375-R suggest that metabolism-related mechanism, such as ferritinophagy, might be triggered, which supported by TEM analysis. Iron storage, transport, ferritinophagy have promising potential to targeted for combining BRAF-targeted therapy reverse MM. Moreover, this is evaluating mechanisms, we our findings contribute improving new drug combinations targeting BRAF metabolism different MM cells.

Language: Английский

Citations

1