Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis

Kang, Rui; Zeng, Ling; Zhu, Shan; Xie, Yangchun; Liu, Jiao; Wen, Qirong; Cao, Lizhi; Xie, Min; Ran, Qitao; Kroemer, Guido; Wang, Haichao; Billiar, Timothy R.; Jiang, Jianxin; Tang, Daolin

doi:10.1016/j.chom.2018.05.009

Cited by 458 publications

(338 citation statements)

References 56 publications

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“…Besides, GPX4 can be inactivated with indirect methods, such as GSH depletion . It should be noted that GPX4 depletion may also sensitize cells to other RCDs (e.g., apoptosis, necroptosis, pyroptosis, etc.). In addition to GPX4, antioxidant proteins like nuclear factor erythroid 2‐related factor 2 (NRF2), and heat shock proteins (HSPs) can also inhibit lipid peroxidation.…”

Section: Basis Of Ferroptosismentioning

confidence: 99%

Recent Progress in Ferroptosis Inducers for Cancer Therapy

et al. 2019

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Ferroptosis is a newly discovered form of regulated cell death that is the nexus between metabolism, redox biology, and human health. Emerging evidence shows the potential of triggering ferroptosis for cancer therapy, particularly for eradicating aggressive malignancies that are resistant to traditional therapies. Recently, there has been a great deal of effort to design and develop anticancer drugs based on ferroptosis induction. Recent advances of ferroptosis‐inducing agents at the intersection of chemistry, materials science, and cancer biology are presented. The basis of ferroptosis is summarized first to highlight the feasibility and characteristics of triggering ferroptosis for cancer therapy. A literature review of ferroptosis inducers (including small molecules and nanomaterials) is then presented to delineate their design, action mechanisms, and anticancer applications. Finally, some considerations for research on ferroptosis inducers are spotlighted, followed by a discussion on the challenges and future development directions of this burgeoning field.

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Section: Basis Of Ferroptosismentioning

confidence: 99%

Recent Progress in Ferroptosis Inducers for Cancer Therapy

et al. 2019

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“…GPx4 has been suggested to negatively regulate pyroptosis both upstream and downstream of the activation of GSDMD. 48 GPx8 interacts with caspase-4 and caspase-11 through disulfide bond formation to inhibit the caspases. 49 GSDMB binds to the CARD of caspase-4, thereby enhancing GSDMD cleavage by the caspase.…”

Section: Regulation Of Pyroptosismentioning

confidence: 99%

Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications

Tsuchiya

2020

Microbiology and Immunology

179

144

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“…Lack of acetylation has been used in studies to try to identify the proportion of HMGB1 that is passively released from damaged/dead cells, as opposed to actively released as part of the inflammatory process . Aerobic glycolysis and lipid peroxidation has been shown to promote HMGB1 release through activation of inflammasomes in sepsis. However, it is unclear whether such metabolic stress induces passive or active release of HMGB1.…”

Section: Getting Hmgb1 Out Of Cells and Into The Circulationmentioning

confidence: 99%

Location is the key to function: HMGB1 in sepsis and trauma-induced inflammation

Deng

Scott

Fan

et al. 2019

Journal of Leukocyte Biology

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129

101

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High mobility group box 1 (HMGB1) is a multifunctional nuclear protein, probably known best as a prototypical alarmin or damage-associated molecular pattern (DAMP) molecule when released from cells. However, HMGB1 has multiple functions that depend on its location in the nucleus, in the cytosol, or extracellularly after either active release from cells, or passive release upon lytic cell death. Movement of HMGB1 between cellular compartments is a dynamic process induced by a variety of cell stresses and disease processes, including sepsis, trauma, and hemorrhagic shock.Location of HMGB1 is intricately linked with its function and is regulated by a series of posttranslational modifications. HMGB1 function is also regulated by the redox status of critical cysteine residues within the protein, and is cell-type dependent. This review highlights some of the mechanisms that contribute to location and functions of HMGB1, and focuses on some recent insights on important intracellular effects of HMGB1 during sepsis and trauma. K E Y W O R D S AIM2, autophagy, caspase-11, DAMPs, pyroptosis 2 NUCLEAR-TO-CYTOPLASM SHUTTLING OF HMGB1 HMGB1 consists of 215 aa residues, and contains 2 HMG DNAbinding domains, designated as A and B boxes, together with a negatively charged C-terminal acidic region. 14 Two nuclear localization sites (NLSs), one located in the A box (aa 28-44) and one in the B box (aa 179-185), control the nuclear localization of HMGB1 under homeostatic states. 14 Posttranslational modifications of NLS sites, including acetylation, phosphorylation, and methylation, regulate the ability of HMGB1 to translocate to the cytoplasm during cellular stress.Once in the cytoplasm HMGB1 can affect multiple inflammatory responses, and can be actively released into the extracellular space and circulation.

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Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis

Cited by 458 publications

References 56 publications

Recent Progress in Ferroptosis Inducers for Cancer Therapy

Recent Progress in Ferroptosis Inducers for Cancer Therapy

Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications

Location is the key to function: HMGB1 in sepsis and trauma-induced inflammation

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