The molecular mechanisms and potential drug targets of ferroptosis in myocardial ischemia–reperfusion injury DOI Creative Commons
Chen-Hua Zhang, Yujie Yan, Qi Luo

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 340, P. 122439 - 122439

Published: Jan. 24, 2024

Myocardial ischemia–reperfusion injury (MIRI), caused by the initial interruption and subsequent restoration of coronary artery blood, results in further damage to cardiac function, affecting prognosis patients with acute myocardial infarction. Ferroptosis is an iron-dependent, superoxide-driven, non-apoptotic form regulated cell death that involved pathogenesis MIRI. characterized accumulation lipid peroxides (LOOH) redox disequilibrium. Free iron ions can induce oxidative stress as a substrate Fenton reaction lipoxygenase (LOX) participate inactivation variety antioxidants including CoQ10 GPX4, destroying balance causing death. The metabolism amino acid, iron, lipids, associated pathways, considered specific hallmark ferroptosis. This review systematically summarizes latest research progress on mechanisms ferroptosis discusses analyzes therapeutic approaches targeting alleviate

Language: Английский

Procyanidins Alleviated Cerebral Ischemia/Reperfusion Injury by Inhibiting Ferroptosis via the Nrf2/HO-1 Signaling Pathway DOI Creative Commons
Lei Chen, Jie Huang,

Zi‐Meng Yao

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(8), P. 3582 - 3582

Published: April 20, 2023

Procyanidins (PCs), which are organic antioxidants, suppress oxidative stress, exhibit anti-apoptotic properties, and chelate metal ions. The potential defense mechanism of PCs against cerebral ischemia/reperfusion injury (CIRI) was investigated in this study. Pre-administration for 7 days a PC enhanced nerve function decreased cerebellar infarct volume mouse middle artery embolization paradigm. In addition, mitochondrial ferroptosis enhanced, exhibited by shrinkage roundness, increased membrane density, reduced or absent ridges. level Fe2+ lipid peroxidation that cause significantly administration. According to the Western blot findings, altered expression proteins associated with ferroptosis, promoting GPX4 SLC7A11 while reducing TFR1, hence inhibiting ferroptosis. Moreover, treatment markedly elevated HO-1 Nuclear-Nrf2. PCs' ability prevent due CIRI Nrf2 inhibitor ML385. Our findings showed protective effect may be achieved via activation Nrf2/HO-1 pathway This study provides new perspective on PCs.

Language: Английский

Citations

25
Berberine modulates gut microbiota to attenuate cerebral ferroptosis induced by ischemia-reperfusion in mice DOI Creative Commons
Xinyu Wang, Jiamin Zhang, Sisi Wang

et al.

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 953, P. 175782 - 175782

Published: May 26, 2023

Ferroptosis was reported to be involved in cerebral ischemia-reperfusion injury (CIRI), on which the effects of berberine (BBR) remain unclear. Moreover, based critical role gut microbiota pleiotropic actions BBR, we hypothesized that BBR can suppress CIRI-induced ferroptosis by modulating microbiota. In this study, results showed obviously attenuated behavioral deficits CIRI mice, accompanied with improved survival rate and neuron damages, as phenocopied dirty cage experiment. The typical morphological changes ferroptotic cells biomarkers were BBR- its fecal microbiota-treated reduced malondialdehyde reactive oxygen species, increased glutathione (GSH). found alter mice decreased abundance Muribaculaceae, Erysipelotrichaceae, Helicobacteraceae, Streptococcaceae Tannerellaceae, but elevated Bacteroidaceae Enterobacteriaceae. KEGG analysis 16S rRNA indicated multiple metabolic pathways including GSH metabolism, altered BBR. Oppositely, antibiotics administration counteracted protective properties Summarily, study revealed therapeutic potential via inhibiting neuronal ferroptosis, upregulated peroxidase 1 (GPX1) possibly involved. BBR-modulated shown play underlying mechanism.

Language: Английский

Citations

23
Progress of Ferroptosis in Ischemic Stroke and Therapeutic Targets DOI Creative Commons
Xinjuan Tian, Xiang Li, Mengtian Pan

et al.

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: Feb. 23, 2024

Ferroptosis is an iron-dependent form of programmed cell death (PCD) and ischemic stroke (IS) has been confirmed to be closely related ferroptosis. The mechanisms ferroptosis were summarized into three interrelated aspects: iron metabolism, lipid peroxide as well glutathione amino acid metabolism. What's more, the causal relationship between IS elucidated by several processes. disruption blood-brain barrier, release excitatory acids, inflammatory response after all lead disorder metabolism antioxidant system. Based on these statements, we reviewed reported effects compounds drugs treating modulating key molecules in Through detailed analysis roles molecules, have also more clearly demonstrated essential effect occurrence so provide new targets ideas for therapeutic IS.

Language: Английский

Citations

15
Ferritinophagy Is Critical for Deoxynivalenol-Induced Liver Injury in Mice DOI
Junze Jiang,

Yongbao Ruan,

Xiaohui Liu

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(12), P. 6660 - 6671

Published: March 19, 2024

Background: Deoxynivalenol (DON) contamination, pervasive throughout all stages of food production and processing, presents a significant threat to human health. The degradation ferritin mediated by nuclear receptor coactivator 4 (NCOA4), termed ferritinophagy, plays crucial role in maintaining iron homeostasis regulating ferroptosis. Aim: This study aims elucidate the ferritinophagy ferroptosis DON-induced liver injury. Methods: Male mice AML12 cells were subjected varying doses DON, serving as vivo vitro models, respectively. Protein expression was assessed using immunofluorescence western blot techniques. Co-immunoprecipitation employed investigate protein–protein interactions. Results: Our findings demonstrate that DON triggers hepatocyte ferritinophagy-dependent manner. Specifically, impedes activation mammalian target rapamycin complex 1 (mTORC1) inhibiting RAC1's binding mTOR, thereby ultimately inducing autophagy. Concurrently, amplifies NCOA4's affinity for facilitating NCOA4 phosphorylation through ataxia-telangiectasia mutated kinase (ATM), thus promoting autophagy-dependent ferritin. Both autophagy inhibition suppression ameliorate Conclusion: concludes facilitates NCOA4-mediated via ATM–NCOA4 pathway, subsequently liver.

Language: Английский

Citations

15
The molecular mechanisms and potential drug targets of ferroptosis in myocardial ischemia–reperfusion injury DOI Creative Commons
Chen-Hua Zhang, Yujie Yan, Qi Luo

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 340, P. 122439 - 122439

Published: Jan. 24, 2024

Myocardial ischemia–reperfusion injury (MIRI), caused by the initial interruption and subsequent restoration of coronary artery blood, results in further damage to cardiac function, affecting prognosis patients with acute myocardial infarction. Ferroptosis is an iron-dependent, superoxide-driven, non-apoptotic form regulated cell death that involved pathogenesis MIRI. characterized accumulation lipid peroxides (LOOH) redox disequilibrium. Free iron ions can induce oxidative stress as a substrate Fenton reaction lipoxygenase (LOX) participate inactivation variety antioxidants including CoQ10 GPX4, destroying balance causing death. The metabolism amino acid, iron, lipids, associated pathways, considered specific hallmark ferroptosis. This review systematically summarizes latest research progress on mechanisms ferroptosis discusses analyzes therapeutic approaches targeting alleviate

Language: Английский

Citations

13