O-GlcNAcylation attenuates ischemia-reperfusion-induced pulmonary epithelial cell ferroptosis via the Nrf2/G6PDH pathway

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 4, 2025

Lung ischemia–reperfusion (I/R) injury is a common clinical pathology associated with high mortality. The pathophysiology of lung I/R involves ferroptosis and elevated protein O-GlcNAcylation levels, while the effect on remains unclear. This research aimed to explore reducing in pulmonary epithelial cells caused by I/R. First, we identified O-GlcNAc transferase 1 (Ogt1) as differentially expressed gene acute injury/acute respiratory distress syndrome (ALI/ARDS) patients, using single-cell sequencing, Gene Ontology analysis (GO analysis) revealed enrichment process. We found time-dependent dynamic alteration during injury. Proteomics proteins enriched multiple redox-related pathways based KEGG annotation. Thus, generated Ogt1-conditional knockout mice that Ogt1 deficiency aggravated ferroptosis, evidenced lipid reactive oxygen species (lipid ROS), malondialdehyde (MDA), Fe2+, well alterations critical expression glutathione peroxidase 4 (GPX4) solute carrier family 7 member 11 (SLC7A11). Consistently, inhibited sensitivity hypoxia/reoxygenation (H/R) injury-induced TC-1 via O-GlcNAcylated NF-E2-related factor-2 (Nrf2). Furthermore, both chromatin immunoprecipitation (ChIP) assay dual-luciferase reporter indicated Nrf2 could bind translation start site (TSS) glucose-6-phosphate dehydrogenase (G6PDH) promote its transcriptional activity. As an important rate-limiting enzyme pentose phosphate pathway (PPP), G6PDH provided mass nicotinamide adenine dinucleotide (NADPH) improve redox state (GSH) eventually led resistance. Rescue experiments proved knockdown or Nrf2-T334A (O-GlcNAcylation site) mutation abolished protective In summary, protect against Nrf2/G6PDH pathway. Our work will provide new basis for therapeutic strategies ischemia–reperfusion-induced

Language: Английский

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Astaxanthin Inhibits Ferroptosis of Hippocampal Neurons in Kainic Acid‐Induced Epileptic Mice by Activating the Nrf2/GPX4 Signaling Pathway

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

ABSTRACT Background Epilepsy, a prevalent neurological disorder, is distinguished by episodic abnormal discharges of neurons within the brain, resulting in transient brain dysfunction. Prior research has identified novel form cell death termed ferroptosis, which intricately linked to initiation and progression epilepsy. It been demonstrated that astaxanthin (AST) can inhibit ferroptosis enhancing activity nuclear factor erythroid 2‐related 2 (Nrf2), thereby providing cytoprotection. Therefore, this study aims investigate whether AST alleviate neuronal epilepsy activating Nrf2/GPX4 pathway, exerting neuroprotective effect. Methods By constructing kainic acid (KA)‐induced mouse model KA‐induced HT22 model, we employed behavioral testing, Western blot analysis, quantitative real‐time reverse transcription qRT‐PCR, ferroptosis‐related assay kits, immunofluorescence staining, other methods. These methodologies were utilized protective effects underlying mechanisms on epileptic mice neurons. Results Our results demonstrate pretreatment alleviates behaviors cognitive impairments mitigates indicators such as lipid peroxidation mitochondrial morphological alterations. This effect appears be mediated activation signaling axis. In vitro studies further revealed confers neuroprotection against death, an abrogated Nrf2 inhibitor. Hence, properties are significantly associated with modulation Nrf2‐mediated corroborated bioinformatics analyses. Conclusion The effectively inhibits both vivo models via pathway. finding suggests holds promise potential therapeutic agent for treatment

Language: Английский

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Acacetin Attenuates Cigarette Smoke Extract-Induced Human Bronchial Epithelial Cell Injury by Activating NRF2/SLC7A11/GPX4 Signaling to Inhibit Ferroptosis

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

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EGCG Alleviates DSS-Induced Colitis by Inhibiting Ferroptosis Through the Activation of the Nrf2-GPX4 Pathway and Enhancing Iron Metabolism

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 547 - 547

Published: Jan. 31, 2025

Background: Ferroptosis is a regulated cell death process linked to various diseases. This study explored whether Epigallocatechin-3-gallate (EGCG), tea-derived antioxidant, could regulate ferroptosis alleviate dextran sulfate sodium (DSS)-induced colitis. Methods: A DSS-induced colitis model was used assess EGCG’s effects. markers, oxidative stress, and iron metabolism were evaluated, alongside Nrf2-GPX4 pathway activation ferritin (FTH/L) expression. Results: Iron dysregulation stress contributed by activating in colonic epithelial cells. EGCG supplementation inhibited ferroptosis, reducing damage. Mechanistically, activated the pathway, enhancing antioxidant defense, improved upregulating Conclusions: effectively suppressed colitis, highlighting its potential as inhibitor therapeutic agent.

Language: Английский

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Helium cold atmospheric pressure plasma reduces erastin induced inflammation and ferroptosis in human gingival fibroblasts

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

Published: March 3, 2025

Oral soft tissue damage can lead to hard in the oral cavity, such as periodontal lesions, periapical disorders, cysts, and tumors. Cold plasma is known alleviate inflammation oxidative stress promote regeneration, yet effects of helium on human gingival cells remain poorly understood. In this study, we examined whether (He) cold atmospheric pressure (CAP) induce anti-inflammatory anti-ferroptotic tissues by ionizing He gas. Erastin treatment followed CAP exposure fibroblast-1 (HGF-1) reduced mRNA expression inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), which are linked inflammatory responses. Additionally, decreased nuclear receptor coactivator 4 (NCOA4) increased glutathione peroxidase (GPX4) expression. Furthermore, mitochondrial membrane potential was restored voltage-dependent anion channel 1 (VDAC1) expression, reactive oxygen species (ROS) levels mitochondria cytoplasm were reduced. These results suggest that may be associated with modulation ROS production reduction ferroptosis, but repair contributes these requires further investigation.

Language: Английский

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Investigating ferroptosis-related genes NFE2L2 in neutrophils for ankylosing spondylitis: therapeutic potential of cassia twigs

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

Published: March 10, 2025

We determined the relationship between ferroptosis and immune cells in ankylosing spondylitis role of Chinese herbal medicine Cassia twigs treating spondylitis. analyzed clinical data on spondylitis, transcriptome data, single-cell sequencing genes related to twigs. Clinical variables AS were selected through logistic regression analysis combined with machine learning. GSEA enrichment performed ferroptosis, drug-related genes, identify key drug targets AS, as well as, cells. Then, cell subtypes analyzed. Finally, interconnections intercellular communication. Five variables, including neutrophils, screened for analysis. The AUC experimental group was 0.859 that validation 0.807. Ferroptosis gene NFE2L2 identified final target AS; it upregulated downregulated control by immunohistochemical verification, both which statistically significant (P < 0.001). Neutrophils divided into two subgroups: high expression low NFE2L2. Through molecular docking, found effectively act important AS. herb can treat acting protein structure

Language: Английский

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Platelet-rich plasma Inhibits Ferroptosis and Inflammation to Alleviate Frozen Shoulder via Activating the CST1/GPX4 Signaling Pathway

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown, P. 110429 - 110429

Published: April 1, 2025

Language: Английский

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Antioxidant Therapies as Emerging Adjuncts in Rheumatoid Arthritis: Targeting Oxidative Stress to Enhance Treatment Outcomes

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2873 - 2873

Published: March 21, 2025

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation and progressive joint destruction. Recent data underscore oxidative stress as primary factor in the pathophysiology of rheumatoid arthritis, intensifying inflammatory processes tissue damage via overproduction reactive oxygen species (ROS) compromised antioxidant defenses. Current therapies, including disease-modifying antirheumatic drugs (DMARDs), primarily target immune dysregulation but fail to address stress, necessitating novel adjunctive treatment strategies. This review explores potential antioxidant-based therapies complementary approaches RA management. Natural compounds such curcumin, resveratrol, sulforaphane, propolis exhibit strong anti-inflammatory antioxidative properties modulating redox-sensitive pathways, nuclear kappa-light-chain-enhancer activated B cells (NF-κB) erythroid 2-related 2(Nrf2)/heme oxygenase (HO-1). N-acetylcysteine (NAC) replenishes intracellular glutathione, enhancing cellular resilience against stress. Additionally, molecular hydrogen (H2) selectively neutralizes harmful ROS, reducing inflammation. The role vitamin supplementation (D, B12, C, K) regulating responses protecting structures also discussed. aims evaluate efficacy clinical applications RA, emphasizing their mitigating improving outcomes. While preliminary findings are promising, further trials needed establish standardized dosing, long-term safety, integration into current protocols.

Language: Английский

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Wuwei Shaji powder alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via the S-sulfhydration of Keap1

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119649 - 119649

Published: April 1, 2025

Language: Английский

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Effects of Acrylamide on Mouse Implantation and Decidualization

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4129 - 4129

Published: April 26, 2025

Acrylamide is a class 2A carcinogen with neurotoxicity and genotoxicity. In addition to industrial production, it ubiquitous in high-temperature heated high-carbohydrate foods. Numerous studies have confirmed the toxicity of ACR on reproduction. Implantation decidualization are crucial processes during establishment pregnancy rodents humans. However, its effect uterine implantation remains poorly understood. The objective this study elucidate mechanism by which affects mice. exposed daily drinking water female mice, dose calculated according body weight After 3 months administration at concentrations 0, 20, 30 mg ACR/kg/d, mice mated male induce pregnancy. Compared control group, treatment significantly reduces number embryo implantations litter size. leads abnormal expression endometrial receptivity-related molecules luminal epithelium day 4 pregnancy, including decrease p-STAT3 level an increase MUC1 MSX1 levels. decidualization-related obviously downregulated ACR. Furthermore, results abnormality oxidative stress- ferroptosis-related protein levels site 5. conclusion, acrylamide can impair mouse disrupting stress ferroptosis.

Language: Английский

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