The Role and Mechanisms of Ubiquitin-Proteasome System-Mediated Ferroptosis in Neurological Disorders

Neuroscience Bulletin, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

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HCMV infection downregulates GPX4 and stimulates lipid peroxidation but does not induce ferroptosis

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

ABSTRACT Human cytomegalovirus (HCMV) modulates numerous cellular pathways to facilitate infection, including key components in iron homeostasis. Iron is essential many processes but, if present excess, drives cell death through ferroptosis. Ferroptosis a process that dependent upon the accumulation of oxidatively damaged phospholipids (lipid peroxides); when these lipid peroxides accumulate membranes, this culminates plasma membrane rupture and eventual lysis. Here, we demonstrate HCMV infection downregulates expression modulator peroxidation, glutathione peroxidase 4 (GPX4). also markedly increased levels within infected cells. Despite marked downregulation GPX4 by HCMV, further inhibition impaired virus replication. Interestingly, overexpression did not reduce production In contrast, peroxide were reduced treatment with ferrostatin-1, ferrous iron-dependent scavenger alkoxyl radicals, indicating role for peroxides. HCMV-infected cells became less sensitive as progressed, requiring substantially higher inhibitors induce ferroptosis compared uninfected This observed difference sensitivity correlated large increase Therefore, stimulation peroxidation likely proceeds pathway independent regulation, but ability stimulate modulating blunted massive during infection. IMPORTANCE intimately linked countless host are modulated coordinated fashion describe HCMV-induced regulation precursor iron-regulated known ferroptosis, human These studies reveal hitherto unidentified changes metabolism mediated decrease despite increases transient intracellular

Язык: Английский

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Effect of eicosapentaenoic acid on innate immune responses in Atlantic salmon cells infected with infectious salmon anemia virus

Virology Journal, Год журнала: 2025, Номер 22(1)

Опубликована: Янв. 9, 2025

Abstract Aquaculture is one of the world's fastest-growing sectors in food production but with multiple challenges related to animal handling and infections. The disease caused by infectious salmon anemia virus (ISAV) leads outbreaks local epidemics, reducing welfare, causing significant economic losses. composition feed has shifted from marine ingredients such as fish oil meal towards a more plant-based diet reduced levels eicosapentaenoic acid (EPA). aim this study was investigate whether low or high EPA affect expression genes innate immune response 48 h after infection ISAV. includes seven experimental groups: ± ISAV various up 200 µM. Analysis RNA sequencing data showed that than 3000 were affected alone (without additional EPA). In cells increasing EPA, 2500 differentially expressed. This indicates concentration have an independent effect on gene virus-infected cells, not observed at lower EPA. Analyses enriched biological processes molecular functions (GO KEGG analysis) revealed had limited impact system alone, many when infected. Several pathways affected, including protein synthesis (ribosomal transcripts), peroxisome proliferator activated receptor (PPAR) signaling, ferroptosis. Cells exposed both concentrations displayed patterns indicating increased formation oxygen radicals cell death via ferroptosis activated. pattern during Atlantic kidney (ASK) highest level (200 μM) without infection. Cell may therefore be mechanism for controlled thus reduction replication there are enough polyunsaturated fatty acids (PUFAs) membrane.

Язык: Английский

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Analysis of differential gene expression in the brain tissue transcriptome of Jiangkou radish piglets infected with porcine pseudorabies virus

SAGE Open Medicine, Год журнала: 2025, Номер 13

Опубликована: Март 1, 2025

Background: The research focused on the effects of pseudorabies virus gene expression in piglet brain tissue. Objectives: goal was to understand changes brains due infection. Design: study used a comparative approach with infected and control groups. Methods: Twelve 2-month-old piglets were divided into virus-infected PBS-treated groups, tissue analyzed after 7 days. Results: Infected showed increased oligodendrocyte counts virus-positive signals. Transcriptomic analysis revealed 269 differentially expressed genes, 149 up-regulated 120 down-regulated. Gene ontology Kyoto Encyclopedia Genes Genomes analyses indicated these genes are involved signal transduction, transmembrane transport, apoptosis, neuroactive ligand–receptor interaction. Quantitative fluorescent PCR validated findings, particularly for related pathways, ferroptosis, IL-17 signaling. Conclusion: provides valuable insights molecular alterations caused by tissue, enhancing our understanding virus’s pathogenic mechanisms.

Язык: Английский

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Taurine Attenuates Neuronal Ferroptosis by CSF-Derived Exosomes of GABABR Encephalitis Through GABABR/NF2/P-YAP Pathway

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

Язык: Английский

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The long noncoding RNA APR attenuates PPRV infection-induced accumulation of intracellular iron to inhibit membrane lipid peroxidation and viral replication

mBio, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

ABSTRACT Peste des petits ruminants virus (PPRV) is an important pathogen that has long been a significant threat to small ruminant productivity worldwide. Iron metabolism vital the host and pathogen. However, mechanism underlying host-PPRV interactions from perspective of iron iron-mediated membrane lipid peroxidation not reported thus far. In this study, we identified novel long-noncoding RNA (lncRNA), APR, impairs PPRV infectivity by sponging miR-3955-5p, negative microRNA (miRNA) directly targets gene encoding ferritin-heavy chain 1 (FTH1) protein. Importantly, demonstrated infection causes aberrant cellular accumulation increasing transferrin receptor (TFRC) expression induces reticulophagy ferroptosis, which benefits replication. Moreover, enhanced localization on endoplasmic reticulum (ER) caused ER damage promoting excess induce reticulophagy. Interestingly, APR decreased infection-induced intracellular Fe 2+ via miR-3955-5p/FTH1 axis ultimately inhibited ferroptosis. Additionally, our results indicate interferon regulatory factor promotes transcription positively regulating promoter activity after infection. Taken together, findings revealed new pattern PPRV-host interactions, involving noncoding regulation, metabolism, iron-related peroxidation, critical for understanding defense against pathogenesis PPRV. IMPORTANCE Many viruses have engage in facilitate their replication pathogenesis. interacts with cells or yet reported. Our data provide first direct evidence promote viral reveal lncRNA, as regulator FTH1 protein expression. increased TFRC expression, more importantly, overload well promoted enhancing induced ferroptosis Furthermore, factor, lncRNA was found decrease protein, thereby attenuating inhibiting present study insight into interaction potential therapeutics

Язык: Английский

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Peste des petits ruminants virus (PPRV) induces ferroptosis via LONP1-mediated mitochondrial GPX4 degradation in cell culture

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

ABSTRACT Peste des petits ruminants virus (PPRV) is an important pathogen that seriously affects the productivity of small worldwide. Ferroptosis a programmed cell death characterized by iron-dependent lipid peroxidation and accumulation reactive oxygen species (ROS). Emerging evidence has demonstrated mitochondria play diverse roles in process ferroptosis, but interaction between ferroptosis during infection remains largely unknown. Here, we demonstrate PPRV induces including Fe 2+ overload, peroxidation, shrinkage mitochondria. Importantly, crucial role PPRV-induced decreased mitochondrial GPX4 Mechanistically, downregulates Lon protease-1 (LONP1) expression, multifaceted enzyme essential for maintaining homeostasis function, which leads to degradation through Nrf2/Keap pathway ROS More importantly, tightly associated with inflammatory responses enhanced replication. Overall, this study first show LONP1-mediated involved infection. IMPORTANCE transient severe immunosuppression host, threatens both livestock endangered susceptible wildlife populations many countries. Despite extensive research, it unknown whether causes what mechanism regulation is. Our data provide direct relationship (LONP1)-mediated dysfunctional consequent induction pathogenesis. via mitochondria, replication levels. Taken together, our research provided new insight into understanding effect on pathogenesis revealed potential therapeutic target antiviral intervention.

Язык: Английский

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Mitochondria-mediated ferroptosis contributes to the inflammatory responses of bovine viral diarrhea virus (BVDV) in vitro

Journal of Virology, Год журнала: 2024, Номер 98(2)

Опубликована: Янв. 16, 2024

Bovine viral diarrhea virus (BVDV) threatens a wide range of domestic and wild cattle population worldwide. BVDV causes great economic loss in industry through its immunosuppression persistent infection. Despite extensive research, the mechanism underlying pathogenesis remains elusive. Our data provide first direct evidence that mitochondria-mediated ferroptosis mitophagy are involved inflammatory responses both biotypes BVDV-infected cells. Importantly, we demonstrate different degrees injury mitochondria may attribute to pathways induced by BVDV. Overall, our findings uncover interaction between infection ferroptosis, which shed novel light on physiological impacts infection, promising therapeutic strategy treat this important infectious disease with worldwide distribution.

Язык: Английский

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Grass carp peroxiredoxin 5 and 6-mediated autophagy inhibit grass carp reovirus replication and mitigate oxidative stress

Fish & Shellfish Immunology, Год журнала: 2024, Номер 146, С. 109419 - 109419

Опубликована: Янв. 30, 2024

Язык: Английский

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Environmental cadmium exposure perturbs systemic iron homeostasis via hemolysis and inflammation, leading to hepatic ferroptosis in common carp (Cyprinus carpio L.)

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 275, С. 116246 - 116246

Опубликована: Март 26, 2024

Cadmium (Cd) pollution is considered a pressing challenge to eco-environment and public health worldwide. Although it has been well-documented that Cd exhibits various adverse effects on aquatic animals, still largely unknown whether how at environmentally relevant concentrations affects iron metabolism. Here, we studied the of environmental exposure (5 50 μg/L) homeostasis possible mechanisms in common carp. The data revealed elevated serum iron, transferrin saturation deposition livers spleens, leading disruption systemic homeostasis. Mechanistic investigations substantiated drove hemolysis by compromising osmotic fragility inducing defective morphology erythrocytes. concurrently exacerbated hepatic inflammatory responses, resulting activation IL6-Stat3 signaling subsequent hepcidin transcription. Notably, elicited ferroptosis through increased burden oxidative stress livers. Taken together, our findings provide evidence mechanistic insight could undermine via erythrotoxicity hepatotoxicity. Further investigation ecological risk assessment other pollutants metabolism-related warranted, especially under realistic scenarios.

Язык: Английский

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