Identification of potential biomarkers of cuproptosis in cerebral ischemia DOI Creative Commons
Lihua Qin,

Xi Cao,

Tengjia Huang

et al.

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: Sept. 18, 2024

Objective Cerebral ischemia can cause mild damage to local brain nerves due hypoxia and even lead irreversible neuronal cell death. However, the underlying pathogenesis of this phenomenon remains unclear. This study utilized bioinformatics explore role cuproptosis in cerebral ischemic disease its associated biomarkers. Method R software identified overlap genes, analyzed Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG), explored hub genes. Expressions localizations genes tissue, cells, immune cells were analyzed, along with predictions protein structures, miRNAs, transcription factors. A network was constructed depicting gene co-expression miRNAs interactions Ferredoxin 1 ( FDX1 ) expression determined using qRT-PCR. Results Ten cuproptosis-related identified, GO analysis revealing involvement acetyl-CoA synthesis, metabolism, mitochondrial function, iron–sulfur cluster binding. KEGG highlighted processes like tricarboxylic acid cycle, pyruvate glycolysis/gluconeogenesis. Using Human Protein Atlas, eight verified tissues, hippocampus, AF22 cells. Lipoyl(octanoyl) transferase LIPT1 ), undetected, while others found mitochondria or both nucleus mitochondria. These differentially expressed , lipoic synthetase LIAS dihydrolipoamide S -acetyltransferase DLAT dehydrogenase E1 component subunit alpha PDHA1 PDHB glutaminase GLS predicted target 111 miRNAs. DLAT, DLD interact 11, 10, 9, 8, 7, 5, 4 factors, respectively. Finally, significantly upregulated hippocampus ovariectomized rats ischemia. Conclusion revealed an association between cuproptosis, identifying potential findings offer new insights into biomarkers for diagnosis, treatment, prognosis ischemia, provide avenues exploration medical intervention targets.

Language: Английский

Cellular and molecular mechanisms of cell damage and cell death in ischemia–reperfusion injury in organ transplantation DOI Creative Commons
George J. Dugbartey

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: March 29, 2024

Ischemia-reperfusion injury (IRI) is a critical pathological condition in which cell death plays major contributory role, and negatively impacts post-transplant outcomes. At the cellular level, hypoxia due to ischemia disturbs metabolism decreases bioenergetics through dysfunction of mitochondrial electron transport chain, causing switch from respiration anaerobic metabolism, subsequent cascades events that lead increased intracellular concentrations Na

Language: Английский

Citations

17
Comprehensive bioinformatics analysis reveals the role of cuproptosis-related gene Ube2d3 in myocardial infarction DOI Creative Commons
Ming Yang, Yucheng Wang,

Liming He

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 19, 2024

Background Myocardial infarction (MI) caused by severe coronary artery disease has high incidence and mortality rates, making its prevention treatment a central challenging aspect of clinical work for cardiovascular practitioners. Recently, researchers have turned their attention to novel mechanism cell death Cu 2+ , cuproptosis. Methods This study integrated data from three MI-related bulk datasets downloaded the Gene Expression Omnibus (GEO) database, identified 16 differentially expressed genes (DEGs) related cuproptosis taking intersection 6378 DEGs obtained differential analysis with 49 cuproptosis-related genes. Four hub genes, Dbt, Dlat, Ube2d1 Ube2d3, were screened out through random forest Lasso analysis. In group, showed low expression, while Ube2d3 exhibited expression. Results Focusing on subsequent functional studies, we confirmed expression in MI group qRT-PCR Western Blot detection after successful construction mouse model left anterior descending (LAD) ligation, further clarified correlation development detecting levels proteins. Moreover, vitro experiments, was be highly oxygen-glucose deprivation (OGD)-treated cardiomyocytes AC16. order clarify role knocked down OGD-treated AC16 cells, Ube2d3’s promoting hypoxia damage cells inducing cuproptosis, as evidenced MTT, TUNEL, LDH release Conclusion summary, our findings indicate that regulates affect progression MI.

Language: Английский

Citations

13
Copper’s dual role: unravelling the link between copper homeostasis, cuproptosis, and cardiovascular diseases DOI
Rajesh Parsanathan

Hypertension Research, Journal Year: 2024, Volume and Issue: 47(5), P. 1440 - 1442

Published: March 11, 2024

Language: Английский

Citations

11
Disulfiram downregulates ferredoxin 1 to maintain copper homeostasis and inhibit inflammation in cerebral ischemia/reperfusion injury DOI Creative Commons
Shuai Yang,

Xudong Li,

Jinhong Yan

et al.

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

Published: July 2, 2024

Abstract In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, transient middle artery occlusion (tMCAO) model C57/BL6 mice was employed. Mice were administered with or without DSF before after tMCAO. Changes infarct volume tMCAO observed using TTC staining. Nissl staining hematoxylin–eosin (he) used observe morphological changes of nerve cells at microscopic level. The inhibitory effect on initial inflammation verified TUNEL assay, apoptosis-related protein detection iron concentration detection. FDX1 is main regulatory death, occurrence death will lead increase HSP70 stress response. Cuproptosis-related proteins downstream factors detected western blotting, immunofluorescence staining, immunohistochemistry. content ions specific kit, while electron microscopy employed examine mitochondrial changes. We found that reduced infarction volume, regulated expression cuproptosis-related proteins, modulated through down regulation expression. Moreover, inhibited HSP70/TLR-4/NLRP3 signaling pathway. Collectively, could Cu homeostasis FDX1, acting HSP70/TLR4/NLRP3 pathway alleviate CI/RI. Accordingly, mitigate responses safeguard integrity, yielding novel therapeutic targets mechanisms for clinical management ischemia–reperfusion injury.

Language: Английский

Citations

11
Edaravone dextranol alleviates ferroptosis, Cuproptosis, and blood-brain barrier damage after acute cerebral infarction DOI
Guishan Jin, Wenfeng Han, Tingting Duan

et al.

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(3)

Published: March 3, 2025

Language: Английский

Citations

2
Inducers of Autophagy and Cell Death: Focus on Copper Metabolism DOI Creative Commons
Weikang Ling, Shuo Li, Yang Zhu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 290, P. 117725 - 117725

Published: Jan. 1, 2025

Language: Английский

Citations

1
Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling DOI Open Access

Canmin Zhu,

Dili Wang,

Chang Chang

et al.

Korean Journal of Physiology and Pharmacology, Journal Year: 2024, Volume and Issue: 28(3), P. 239 - 252

Published: April 29, 2024

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury.In this study, we explored the beneficial effects dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation cerebral ischemia/reperfusion injury.Sprague-Dawley rats were subjected to middle artery occlusion (MCAO) for 1.5 h reperfusion 24 establish a rat model injury.Dexmedetomidine (9 g/kg) was administered 30 min after MCAO through intravenous injection, SB203580 (a p38 MAPK inhibitor, 200 injected intraperitoneally before MCAO.Brain damages evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin Nissl water content assessment.BBB permeability examined Evans blue staining.Expression levels claudin-5, zonula occludens-1, occludin, matrix metalloproteinase-9 (MMP-9) as well M1/M2 phenotypes-associated markers assessed using immunofluorescence, RT-qPCR, Western blotting, gelatin zymography.Enzyme-linked immunosorbent assay used examine inflammatory cytokine levels.We found that or attenuated infarct volume, edema, BBB permeability, neuroinflammation, promoted M2 microglial polarization injury.Increased MMP-9 activity injury inhibited SB203580.Dexmedetomidine activation ERK, JNK, pathways.Moreover, JNK reversed protective against injury.Overall, ameliorated alleviating promoting experimental inhibiting pathways.

Language: Английский

Citations

5
CircSpna2 attenuates cuproptosis by mediating ubiquitin ligase Keap1 to regulate the Nrf2‐Atp7b signalling axis in depression after traumatic brain injury in a mouse model DOI Creative Commons

Mengran Du,

Jiayuanyuan Fu,

Jie Zhang

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(11)

Published: Nov. 1, 2024

Language: Английский

Citations

5
Dexmedetomidine Inhibits Ferroptosis by Regulating the SRY‐Box Transcription Factor 9/Divalent Metal Transporter‐1 Axis to Alleviate Cerebral Ischemia/Reperfusion Injury DOI Open Access
Zhen Liu,

Qionghua Liu,

Xuekang Zhang

et al.

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(1)

Published: Jan. 1, 2025

Cerebral ischemia/reperfusion injury (IRI) is pathologically associated with ferroptosis. Dexmedetomidine (Dex) exerts neuroprotective activity after cerebral IRI. Our work focused on probing the pharmacologic effect of Dex ferroptosis during IRI and mechanisms involved. models were established by oxygen-glucose deprivation/reoxygenation (OGD/R) middle artery occlusion (MCAO). 2,3,5-Triphenyltetrazolium chloride (TTC) staining was utilized to detect infarct size mNSS performed evaluate neurologic deficits. Brain pathologic changes analyzed HE staining. Lipid peroxidation level detected C11-BODIPY staining, Fe

Language: Английский

Citations

0
The Role of the Sirt1/Foxo3a Pathway in Mitigating Myocardial Ischemia–Reperfusion Injury by Dexmedetomidine DOI Creative Commons
Hanlin Ding,

Danyong Liu,

Jianfeng He

et al.

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(4)

Published: April 1, 2025

ABSTRACT Myocardial ischemia–reperfusion injury (MIRI) significantly affects the prognosis of cardiac surgery patients. The anesthetic dexmedetomidine (Dex) has shown protective effects against in cardiomyocytes; however, its exact mechanism remains unclear. In this study, hypoxia/reoxygenation (H/R) and ischemia/reperfusion (I/R) models were used to investigate Dex on H9c2 cells MIRI mice. roles Sirtuin 1/Forkhead box O3a (Sirt1/FoxO3a) pathway explored using Sirt1 inhibitor EX527 FoxO3a gene silencing. Results showed that H/R reduced cell viability, increased Lactate Dehydrogenase (LDH) leakage, elevated reactive oxygen species (ROS) production. pretreatment reversed these effects. Additionally, expression Bcl‐2‐associated X protein/B‐cell lymphoma 2 (Bax/Bcl‐2), cleaved caspase‐3, Beclin‐1, microtubule‐associated protein 1A/1B‐light chain 3B (LC3B), inhibiting apoptosis autophagy while increasing p62, Sirt1, FoxO3a. abolished by or mouse model, decreased serum LDH Creatine Kinase‐MB (CK‐MB) levels, myocardial infarct size injury, improved left ventricular ejection fraction (LVEF) fractional shortening (LVFS). These markedly EX527. findings indicate alleviates restoring activating

Language: Английский

Citations

0