The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Год журнала: 2023, Номер 4(1)

Опубликована: Окт. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Язык: Английский

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Neurotoxicity of manganese via ferroptosis induced by redox imbalance and iron overload

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 278, С. 116404 - 116404

Опубликована: Май 4, 2024

Manganese (Mn) is an essential trace element for maintaining bodily functions. Excessive exposure to Mn can pose serious health risks humans and animals, particularly the nervous system. While has been implicated as a neurotoxin, exact mechanism of its toxicity remains unclear. Ferroptosis form programmed cell death that results from iron-dependent lipid peroxidation. It plays role in various physiological pathological cellular processes may be closely related Mn-induced neurotoxicity. However, ferroptosis neurotoxicity not thoroughly investigated. Therefore, this study aims investigate Using bioinformatics, we identified significant changes genes associated with Mn-exposed animal models. We then evaluated at both levels. Our findings suggest causes weight loss system damage mice. In vitro vivo experiments have shown increases malondialdehyde, reactive oxygen species, ferrous iron, while decreasing glutathione adenosine triphosphate. These leads increase peroxidation disrupts iron metabolism, resulting oxidative stress injury ferroptosis. Furthermore, assessed expression levels proteins mRNAs ferroptosis, confirming involvement

Язык: Английский

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Downregulation of FcRn promotes ferroptosis in herpes simplex virus-1-induced lung injury

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Янв. 6, 2025

Herpes simplex virus type I (HSV-1) infection is associated with lung injury; however, no specific treatment currently available. In this study, we found a significant negative correlation between FcRn levels and the severity of HSV-1-induced injury. HSV-1 increases methylation promoter, which suppresses expression by upregulating DNMT3b expression. Analysis promoter revealed that -1296- to -919-bp region key regulatory region, CG site at -967/-966 bp being critical site. The transcription factor JUN binds increase transcription; its activity was significantly inhibited overexpression. Moreover, 5-Aza-2 effectively reduced injury ferroptosis. Transcriptomic sequencing ferroptosis pathway highly activated in tissues FcRn-knockout mice via p53/SLC7A11 pathway. Furthermore, vivo experiments showed knockout aggravated epithelial cell inflammation promoting ferroptosis; effect reversed inhibitor. Thus, suppressed through promoted These findings reveal novel molecular mechanism underlying viral suggest potential therapeutic strategies for targeting FcRn.

Язык: Английский

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A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Ноя. 9, 2023

Abstract According to a paper released and submitted WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as direct result. Hepatitis B virus (HBV) hepatitis C (HCV), D (HDV) all play critical roles the pathogenesis hepatocellular carcinoma (HCC), despite rising prevalence HCC due non-infectious causes. Liver cirrhosis are devastating consequences HBV HCV infections, which widespread worldwide. Associated high mortality rate, these infections cause about 1.3 million annually primary globally. In addition causing insertional mutations viral gene integration, epigenetic alterations inducing chronic immunological dysfunction methods viruses turn hepatocytes into cancerous ones. While expanding our knowledge illness, identifying pathways also give possibilities for novel diagnostic treatment methods. Nuclear factor erythroid 2-related 2 (NRF2) activation is gaining popularity option oxidative stress (OS), inflammation, metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression linked HCC, providing more evidence HCC. This aberrant signaling drives cell proliferation, initiates angiogenesis invasion, imparts drug resistance. As result, this master regulator may promising target addition, common effect contributes pathogenesis, development, chronicity infection. However, certain suppress activity, helpful maintaining cellular homeostasis. paper, we discussed influence deregulation on life cycle associated HCV. We summed up mechanisms modulation deregulated viruses. Moreover, describe molecular mechanism modulated cancer, stem cells (LCSCs), caused

Язык: Английский

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Ginsenoside Rg5, a potent agonist of Nrf2, inhibits HSV-1 infection-induced neuroinflammation by inhibiting oxidative stress and NF-κB activation

Journal of Ginseng Research, Год журнала: 2024, Номер 48(4), С. 384 - 394

Опубликована: Фев. 6, 2024

Herpes simplex virus type 1 (HSV-1), known to latently infect the host's trigeminal ganglion, can lead severe herpes encephalitis or asymptomatic infection, potentially contributing neurodegenerative diseases like Alzheimer's. The generates reactive oxygen species (ROS) that significantly impact viral replication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related 2 (Nrf2), an oxidative stress regulator, prevent treat HSV-1 infection by activating passive defense response in early stages of infection. Our study investigated antiviral effects ginsenoside Rg5, Nrf2 activator, on several host cell signaling pathways. We found inhibited activity cells, induced ROS/NF-κB signaling, triggered inflammatory cytokines. However, treatment with Rg5 reduced cytokines NRF2 induction. Interestingly, inhibitor ML385 suppressed expression NAD(P)H quinone oxidoreductase 1(NQO1) enhanced KEAP1 infected cells. This led reversal VP16 inhibition, a protein associated thereby promoting replication. These findings suggest for first time may serve as against could be novel therapeutic agent HSV-1-induced neuroinflammation.

Язык: Английский

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Immunopathology of herpes simplex virus‐associated neuroinflammation: Unveiling the mysteries

Reviews in Medical Virology, Год журнала: 2023, Номер 34(1)

Опубликована: Ноя. 20, 2023

The immunopathology of herpes simplex virus (HSV)-associated neuroinflammation is a captivating and intricate field study within the scientific community. HSV, renowned for its latent infection capability, gives rise to spectrum neurological expressions, ranging from mild symptoms severe encephalitis. enigmatic interplay between host's immune responses profoundly shapes outcome these infections. This review delves into multifaceted reactions triggered by HSV neural tissues, intricately encompassing innate adaptive immunity. Furthermore, this analysis delicate equilibrium defence potential immunopathology-induced damage. It meticulously dissects roles diverse cells, cytokines, chemokines, unravelling intricacies modulation subsequent effects. By exploring HSV's manipulation exploitation mechanisms, endeavours unveil enigmas surrounding HSV-associated neuroinflammation. comprehensive understanding enhances our grasp viral pathogenesis holds promise pioneering therapeutic strategies designed mitigate ramifications

Язык: Английский

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Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia

Virologica Sinica, Год журнала: 2023, Номер 39(1), С. 31 - 43

Опубликована: Сен. 9, 2023

Human endogenous retroviruses (HERVs) are remnants of retroviral infections in human germline cells from millions years ago. Among these, ERVW-1 (also known as HERV-W-ENV, ERVWE1, or ENVW) encodes the envelope protein HERV-W family, which contributes to pathophysiology schizophrenia. Additionally, neuropathological studies have revealed cell death and disruption iron homeostasis brains individuals with Here, our bioinformatics analysis showed that differentially expressed genes prefrontal cortex RNA microarray dataset (GSE53987) were mainly related ferroptosis its associated pathways. Clinical data demonstrated significantly lower expression levels ferroptosis-related genes, particularly Glutathione peroxidase 4 (GPX4) solute carrier family 3 member 2 (SLC3A2), schizophrenia patients compared normal controls. Further in-depth analyses a significant negative correlation between GPX4/SLC3A2 Studies indicated increased levels, malondialdehyde (MDA), transferrin receptor 1 (TFR1) while decreasing glutathione (GSH) triggering loss mitochondrial membrane potential, suggesting can induce ferroptosis. Ongoing research has shown reduced GPX4 SLC3A2 by inhibiting their promoter activities. Moreover, Ferrostatin-1 (Fer-1), inhibitor, reversed accumulation potential loss, well restored expressions markers GSH, MDA, TFR1 induced ERVW-1. In conclusion, could promote downregulating SLC3A2, revealing novel mechanism neuronal

Язык: Английский

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TRIM21 Promotes Oxidative Stress and Ferroptosis through the SQSTM1-NRF2-KEAP1 Axis to Increase the Titers of H5N1 Highly Pathogenic Avian Influenza Virus

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3315 - 3315

Опубликована: Март 14, 2024

Tripartite motif-containing protein 21 (TRIM21) is involved in signal transduction and antiviral responses through the ubiquitination of targets. TRIM21 was reported to be related imbalance host cell homeostasis caused by viral infection. Our studies indicated that H5N1 highly pathogenic avian influenza virus (HPAIV) infection up-regulated expression A549 cells. Western blot qPCR results showed knockdown alleviated oxidative stress ferroptosis induced HPAIV promoted activation antioxidant pathways. Co-IP regulating SQSTM1-NRF2-KEAP1 axis increasing SQSTM1 K63-linked polyubiquitination under condition In addition, attenuated inhibitory effect NAC on titers enhanced promoting agonist Erastin titers. findings provide new insight into role

Язык: Английский

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Ferritin: Significance in viral infections

Reviews in Medical Virology, Год журнала: 2024, Номер 34(2)

Опубликована: Март 1, 2024

As an indispensable trace element, iron is essential for many biological processes. Increasing evidence has shown that virus infection can perturb metabolism and play a role in the occurrence development of viral infection-related diseases. Ferritin plays crucial maintaining body's homoeostasis. It important protein to stabilise balance cells. 24-mer hollow storage composed two subunits: ferritin heavy chain light chain. was reported not only intra-cellular protein, but also pathogenic mediator enhances inflammatory process stimulates further pathway, which key member vicious cycle perpetuate. exerts immuno-suppressive pro-inflammatory functions during infection. In this review, we describe detail basic information first section, including its structural features, regulation ferritin. second part, focus on diseases molecular mechanisms by regulates The last section briefly outlines potential antiviral therapy. Given importance infection, understanding helps us understand relationship between metabolic dysfunction provides new direction therapeutic drugs.

Язык: Английский

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Metabolomics combined with network pharmacology reveals a role for astragaloside IV in inhibiting enterovirus 71 replication via PI3K-AKT signaling

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 10, 2024

Язык: Английский

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