COVID-19 Causes Ferroptosis and Oxidative Stress in Human Endothelial Cells

Antioxidants, Год журнала: 2023, Номер 12(2), С. 326 - 326

Опубликована: Янв. 31, 2023

Oxidative stress and endothelial dysfunction have been shown to play crucial roles in the pathophysiology of COVID-19 (coronavirus disease 2019). On these grounds, we sought investigate impact on lipid peroxidation ferroptosis human cells. We hypothesized that oxidative induced by cells could be linked outcome. Thus, collected serum from patients hospital admission, incubated sera with cells, comparing effects generation reactive oxygen species (ROS) between who survived did not survive. found non-survivors significantly increased peroxidation. Moreover, markedly regulated expression levels main markers ferroptosis, including GPX4, SLC7A11, FTH1, SAT1, a response was rescued silencing TNFR1 Taken together, our data indicate survive triggers

Язык: Английский

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Implication of COVID-19 on Erythrocytes Functionality: Red Blood Cell Biochemical Implications and Morpho-Functional Aspects

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(4), С. 2171 - 2171

Опубликована: Фев. 16, 2022

Several diseases (such as diabetes, cancer, and neurodegenerative disorders) affect the morpho-functional aspects of red blood cells, sometimes altering their normal metabolism. In this review, hematological changes are evaluated, with particular focus on morphology metabolic erythrocytes. Changes in functionality such cells may, fact, help provide important information about disease severity progression. The viral infection causes significant damage to that altered size, rigidity, distribution width. Lower levels hemoglobin anemia have been reported several studies, an alteration concentration antioxidant enzymes has shown promote a dangerous state oxidative stress cells. Patients severe COVID-19 showed increase changes, indicating progressive worsening progressed. Therefore, monitored alterations patients may play role management prevent risk course disease. Finally, erythrocytes blood, general, be one condition known Long COVID.

Язык: Английский

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When ferroptosis meets pathogenic infections

Trends in Microbiology, Год журнала: 2022, Номер 31(5), С. 468 - 479

Опубликована: Дек. 7, 2022

Язык: Английский

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GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection

The Journal of Experimental Medicine, Год журнала: 2022, Номер 219(11)

Опубликована: Сен. 7, 2022

Cellular necrosis during Mycobacterium tuberculosis (Mtb) infection promotes both immunopathology and bacterial dissemination. Glutathione peroxidase-4 (Gpx4) is an enzyme that plays a critical role in preventing iron-dependent lipid peroxidation–mediated cell death (ferroptosis), process previously implicated the necrotic pathology seen Mtb-infected mice. Here, we document altered GPX4 expression, glutathione levels, peroxidation patients with active assess of this pathway mice genetically deficient or overexpressing Gpx4. We found Gpx4-deficient infected Mtb display substantially increased lung burdens, while transgenic show decreased loads necrosis. Moreover, macrophages exhibited enhanced upon vitro, outcome suppressed by inhibitor, ferrostatin-1. These findings provide support for ferroptosis Mtb-induced implicate Gpx4/GSH axis as target host-directed therapy tuberculosis.

Язык: Английский

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Herpes Simplex Virus 1-Induced Ferroptosis Contributes to Viral Encephalitis

mBio, Год журнала: 2022, Номер 14(1)

Опубликована: Дек. 12, 2022

Herpes simplex virus 1 (HSV-1) is a DNA belonging to the family Herpesviridae. HSV-1 infection causes severe neurological disease in central nervous system (CNS), including encephalitis. Ferroptosis nonapoptotic form of programmed cell death that contributes different inflammatory diseases. However, whether induces ferroptosis CNS and role viral pathogenesis remain unclear. Here, we demonstrate ferroptosis, as hallmarks Fe2+ overload, reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, mitochondrion shrinkage, are observed HSV-1-infected cultured human astrocytes, microglia cells, murine brains. Moreover, enhances E3 ubiquitin ligase Keap1 (Kelch-like ECH-related protein 1)-mediated ubiquitination degradation nuclear factor E2-related 2 (Nrf2), transcription regulates expression antioxidative genes, thereby disturbing cellular redox homeostasis promoting ferroptosis. Furthermore, HSV-1-induced tightly associated with process encephalitis mouse model, ferroptosis-activated upregulation prostaglandin-endoperoxide synthase (PTGS2) prostaglandin E2 (PGE2) plays an important HSV-1-caused inflammation Importantly, inhibition by inhibitor or proteasome suppress Nrf2 effectively alleviated Together, our findings interaction between provide novel insights into IMPORTANCE In current study, ROS GSH all which brains infected HSV-1. Keap1-dependent degradation, results substantial reductions levels antiferroptotic genes downstream Nrf2, PTGS2 PGE2 either alleviates neuro-damage mice. Overall, uncover shed light on physiological impacts encephalitis, promising therapeutic strategy treat this infectious worldwide distribution.

Язык: Английский

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Revisiting Regulated Cell Death Responses in Viral Infections

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(13), С. 7023 - 7023

Опубликована: Июнь 24, 2022

The fate of a viral infection in the host begins with various types cellular responses, such as abortive, productive, latent, and destructive infections. Apoptosis, necroptosis, pyroptosis are three major regulated cell death mechanisms that play critical roles response. Cell shrinkage, nuclear condensation, bleb formation, retained membrane integrity all signs osmotic imbalance-driven cytoplasmic swelling early damage necroptosis pyroptosis. Caspase-driven apoptotic demise is considered many circumstances an anti-inflammatory, some pathogens hijack signaling routes to initiate targeted attack against host. In this review, selected by which viruses interfere were discussed in-depth illustrated compiling general principles virus–host-specific molecule interactions.

Язык: Английский

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New Insights into the Role of Ferroptosis in Cardiovascular Diseases

Cells, Год журнала: 2023, Номер 12(6), С. 867 - 867

Опубликована: Март 10, 2023

Cardiovascular diseases (CVDs) are the principal cause of disease burden and death worldwide. Ferroptosis is a new form regulated cell mainly characterized by altered iron metabolism, increased polyunsaturated fatty acid peroxidation reactive oxygen species, depletion glutathione inactivation peroxidase 4. Recently, series studies have indicated that ferroptosis involved in cardiac vascular cells has key impact on mechanisms leading to CVDs such as ischemic heart disease, ischemia/reperfusion injury, cardiomyopathies, failure. In this article, we reviewed molecular mechanism current understanding pathophysiological role some cardiomyopathies. Moreover, comprehension machinery governing cardiomyocytes may provide insights into preventive therapeutic strategies CVDs.

Язык: Английский

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SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis

Redox Biology, Год журнала: 2023, Номер 63, С. 102752 - 102752

Опубликована: Май 23, 2023

Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced death. Previous studies have observed enhanced ROS level signs ferroptosis SARS-CoV-2 infected cells specimens patients COVID-19, but exact mechanism is not clear yet. Here, we find ORF3a sensitizes to via Keap1-NRF2 axis. promotes degradation NRF2 through recruiting Keap1, thereby attenuating cellular resistance oxidative stress facilitated ferroptotic Our study uncovers that functions positive regulator ferroptosis, might explain damage organs COVID-19 imply potential treatment.

Язык: Английский

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SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1157 - 1157

Опубликована: Янв. 18, 2024

The pandemic of coronavirus disease 2019 (COVID-19) has been the foremost modern global public health challenge. airway is primary target in severe acute respiratory distress syndrome 2 (SARS-CoV-2) infection, with substantial cell death and lung injury being signature hallmarks exposure. viral factors that contribute to remain incompletely understood. Thus, this study investigated role open reading frame 7b (Orf7b), an accessory protein virus, causing injury. In screening proteins, we identified Orf7b as one major mediates epithelial death. Overexpression leads apoptosis ferroptosis cells, inhibitors ablate Orf7b-induced upregulates transcription regulator, c-Myc, which integral activation pathways. Depletion c-Myc alleviates both apoptotic ferroptotic deaths mouse models. Our suggests a attributable COVID-19 exposure, supporting it potential therapeutic target.

Язык: Английский

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Human transferrin receptor can mediate SARS-CoV-2 infection

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(10)

Опубликована: Фев. 26, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of disease-19 patients, although some do not express angiotensin-converting enzyme-2 (ACE2), a known receptor SARS-CoV-2, implying the presence alternative receptors and/or co-receptors. Here, we show that ubiquitously distributed human transferrin (TfR), which binds to diferric traffic between membrane and endosome for iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, mouse TfR, interacts with Spike protein high affinity (K D ~2.95 nM) endocytosis. TfR knock-down (TfR-deficiency is lethal) overexpression inhibit promote infection, respectively. Humanized expression enables baby hamster kidney cells C57 mice, are be insusceptible virus Soluble Tf, designed peptides blocking TfR-Spike interaction anti-TfR antibody significant anti-COVID-19 effects cell monkey models. Collectively, this report indicates receptor/co-receptor mediating entry infectivity by likely using trafficking pathway.

Язык: Английский

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