GPx4 in Bacterial Infection and Polymicrobial Sepsis: Involvement of Ferroptosis and Pyroptosis

Zhu, Hong; Santo, Arben; Jia, Zhenquan; Li, Y. Robert

doi:10.20455/ros.2019.835

Cited by 58 publications

(56 citation statements)

References 36 publications

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“…Mechanistically, D3T suppresses LPS-induced proinflammatory cytokine gene expression in an Nrf2-dependent manner in inflammatory cells and such suppression stems, at least partly, from D3T-mediated inhibition of the NF-κB pathway. In addition, D3T-mediated upregulation of cellular antioxidants, particularly GPx4 [9], and downregulation of cellular iron may also lead to suppression of ferroptosis and pyroptosis, two critical pathophysiological events in sepsis [27] (Figure 11).…”

Section: Discussionmentioning

confidence: 99%

3H-1,2-Dithiole-3-Thione as a Potentially Novel Therapeutic Compound for Sepsis Intervention

Li¹,

Jia²,

Zhu

2019

ROS

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Through the history of modern medicine, bioactive components in natural products have been either employed directly as medicines or used as prototypes for synthetic drug development. This brief Research Highlights paper considers 3H-1,2-dithiole-3-thione (D3T), a member of the 1,2-dithiole-3-thiones—compounds which may naturally occur in cruciferous vegetables. Among 1,2-dithiole-3-thiones, D3T is the most potent member with regard to the capacity of inducing tissue defenses against oxidative and inflammatory stress. Oxidative and inflammatory stress is a major pathophysiological process involved in numerous human disorders, including cancer, cardiovascular diseases, neurodegeneration, and sepsis, to name just a few. This article surveys recent major research findings on D3T as an inducer of tissue antioxidative and antiinflammatory defenses and as a potential therapeutic modality for sepsis intervention.

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Section: Discussionmentioning

confidence: 99%

3H-1,2-Dithiole-3-Thione as a Potentially Novel Therapeutic Compound for Sepsis Intervention

Li¹,

Jia²,

Zhu

2019

ROS

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“…Both of these studies suggest that, unlike other types of necrotic cell death, ferroptosis induction favors pathogen dissemination or virulence and not host defense. That ferroptosis might worsen the outcome of bacterial infections is also supported by a new study that showed that GPX4 deficiency in myeloid cell increases the severity of polymicrobial sepsis in mice, since GPX4 was necessary to block phospholipase C gamma 1 (PLCG1)‐mediated GSDMD activity and pyroptosis 93 . However due the recent emergence of the ferroptosis pathway and the lack of genetic tools, we currently know too little about this pathway to definitely conclude that ferroptosis cannot be protective as well.…”

Section: Programmed Cell Death During Bacterial Infectionmentioning

confidence: 98%

Cross talk between intracellular pathogens and cell death

Demarco

Chen

Brož

2020

Immunological Reviews

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Infections with bacterial pathogens often results in the initiation of programmed cell death as part of the host innate immune defense, or as a bacterial virulence strategy. Induction of host cell death is controlled by an elaborate network of innate immune and cell death signaling pathways and manifests in different morphologically and functionally distinct forms of death, such as apoptosis, necroptosis, NETosis and pyroptosis. The mechanism by which host cell death restricts bacterial replication is highly cell‐type and context depended, but its physiological importance is highlighted the diversity of strategies bacterial pathogens use to avoid induction of cell death or to block cell death signaling pathways. In this review, we discuss the latest insights into how bacterial pathogens elicit and manipulate cell death signaling, how different forms of cell death kill or restrict bacteria and how cell death and innate immune pathway cross talk to guard against pathogen‐induced inhibition of host cell death.

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“…Peculiarly, ferroptosis causes irreversible alteration of mitochondrial morphology ( Twig & Shirihai, 2011 ). Furthermore, substantial evidence revealed that ferroptosis is involved in bacterial infection induced cell death and tissue damage ( Zhu et al, 2019 ). For instance, Pseudomonas aeruginosa was shown to trigger ferroptosis in host bronchial epithelium through generating lipoxygenase, that is involved in the initiation of lipid peroxidation, by oxidizing host arachidonic acid–phosphatidylethanolamines ( Dar et al, 2018 ).…”

Section: The Role Of Ferroptosismentioning

confidence: 99%

Mitochondria and microbiota dysfunction in COVID-19 pathogenesis

et al. 2020

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Highlights Mitochondria are the hub of cellular oxidative homeostasis. Mitochondria are the major source of reactive oxygen species (ROS). Extracellular mitochondria are found in blood, in circulating platelets and vesicles. COVID-19 pathogenesis is aggravated by the hyper- inflammatory state. Inflammation activates events leading to microbiota & mitochondrial oxidative damage. Mitochondrial damage contributes to coagulopathy, ferroptosis & microbial dysbiosis. Blood & platelet mitochondria dysfunction may accelerate systemic coagulopathy events. Targeting mitochondria dysfunction may provide useful therapeutic strategies against COVID-19 pathogenesis.

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GPx4 in Bacterial Infection and Polymicrobial Sepsis: Involvement of Ferroptosis and Pyroptosis

Cited by 58 publications

References 36 publications

3H-1,2-Dithiole-3-Thione as a Potentially Novel Therapeutic Compound for Sepsis Intervention

3H-1,2-Dithiole-3-Thione as a Potentially Novel Therapeutic Compound for Sepsis Intervention

Cross talk between intracellular pathogens and cell death

Mitochondria and microbiota dysfunction in COVID-19 pathogenesis

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