Glutathione peroxidase 8 negatively regulates caspase‐4/11 to protect against colitis

Hsu, Jye‐Lin; Chou, Jen–Wei; Chen, Tzu‐Fan; Hsu, Jeh‐Ting; Su, Fang‐Yi; Lan, Joung‐Liang; Wu, Po‐Chang; Hu, Chun‐Mei; Lee, Eva Yhp; Lee, Wen‐Hwa

doi:10.15252/emmm.201809386

Cited by 37 publications

(29 citation statements)

References 47 publications

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“…Interestingly, the interaction between Prdx-4 and caspase-1 takes place in extracellular vesicles, implying its involvement in inflammasome-mediated propagation of inflammatory signals between cells [101]. In the second study, glutathione peroxidase (GPx)-8 was shown to inhibit the activation of another pyroptosis-related protease, caspase-4/11 [102]. GPx8 binds covalently to caspase-4/11 through a disulfide linkage between Cys-79 of GPx8 and Cys-118 of caspase-4, thereby attenuating caspase-4/11 oligomerization and activation.…”

Section: Inflammasome-caspase-1 Pathwaymentioning

confidence: 99%

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Oxidants, Antioxidants and Thiol Redox Switches in the Control of Regulated Cell Death Pathways

Benhar

2020

Antioxidants

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It is well appreciated that biological reactive oxygen and nitrogen species such as hydrogen peroxide, superoxide and nitric oxide, as well as endogenous antioxidant systems, are important modulators of cell survival and death in diverse organisms and cell types. In addition, oxidative stress, nitrosative stress and dysregulated cell death are implicated in a wide variety of pathological conditions, including cancer, cardiovascular and neurological diseases. Therefore, much effort is devoted to elucidate the molecular mechanisms linking oxidant/antioxidant systems and cell death pathways. This review is focused on thiol redox modifications as a major mechanism by which oxidants and antioxidants influence specific regulated cell death pathways in mammalian cells. Growing evidence indicates that redox modifications of cysteine residues in proteins are involved in the regulation of multiple cell death modalities, including apoptosis, necroptosis and pyroptosis. In addition, recent research suggests that thiol redox switches play a role in the crosstalk between apoptotic and necrotic forms of regulated cell death. Thus, thiol-based redox circuits provide an additional layer of control that determines when and how cells die.

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Section: Inflammasome-caspase-1 Pathwaymentioning

confidence: 99%

“…GPx8 binds covalently to caspase-4/11 through a disulfide linkage between Cys-79 of GPx8 and Cys-118 of caspase-4, thereby attenuating caspase-4/11 oligomerization and activation. This mechanism may account for the ability of GPx8 to protect against colitis [102].…”

Section: Inflammasome-caspase-1 Pathwaymentioning

confidence: 99%

Oxidants, Antioxidants and Thiol Redox Switches in the Control of Regulated Cell Death Pathways

Benhar

2020

Antioxidants

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“…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. 50 Oxidative stress has also been proposed to augment the cleavage of GSDMD by caspase-1, which enhances pyroptosis.…”

Section: Regulation Of Pyroptosismentioning

confidence: 99%

“…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 50 .…”

Section: Pyroptosismentioning

confidence: 99%

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

Tsuchiya

2020

Microbiology and Immunology

179

144

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“…BMDMs were isolated from mice and differentiated for 5-6 days, following standard procedures 31 . Adherent BMDMs were cultured overnight at a density of 1 × 10 6 cells per ml before being treated with 5, 2.5, 0.5, or 0.25% WE (equivalent to 12.5, 6.25, 1.25, or 0.625 mg MDP residue per ml, respectively) or with the indicated chemicals for 6 h. The cells were then stimulated with TLR ligands at the indicated concentrations 32 .…”

Section: Methodsmentioning

confidence: 99%

A systematic identification of anti-inflammatory active components derived from Mu Dan Pi and their applications in inflammatory bowel disease

Chen

Hsu

et al. 2020

Sci Rep

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Mu Dan Pi (MDP), also known as Moutan Cortex Radicis, is a traditional Chinese medicine used to treat autoimmune diseases. However, the impact of MDP and its principal active compounds on inflammatory bowel disease (IBD) is uncertain. This study therefore systemically assessed the anti-inflammatory effects of MDP and its known active compounds in IBD. The anti-inflammatory activities of water extract and individual compounds were screened by NF-κB and interferon regulatory factor (IRF) reporter assays in THP-1 cells induced with either Toll-like receptor or retinoic acid inducible gene I/melanoma differentiation-associated gene 5 activators and further verified in bone marrow-derived macrophages. MDP water extract significantly inhibited the activation of NF-κB and IRF reporters, downstream signaling pathways and the production of IL-6 and TNF-α, in a dose-dependent manner. Among 5 known active components identified from MDP (1,2,3,4,6-penta-O-galloyl-β-d-glucose [PGG], gallic acid, methyl gallate, paeoniflorin, and paeonol), PGG was the most efficient at inhibiting both reporters (with an IC50 of 5–10 µM) and downregulating IL-6 and TNF-α. Both MDP powder for clinical use and MDP water extract, but not PGG, reduced colitis and pathological changes in mice. MDP and its water extract show promise as a novel therapy for IBD patients.

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Glutathione peroxidase 8 negatively regulates caspase‐4/11 to protect against colitis

Cited by 37 publications

References 47 publications

Oxidants, Antioxidants and Thiol Redox Switches in the Control of Regulated Cell Death Pathways

Oxidants, Antioxidants and Thiol Redox Switches in the Control of Regulated Cell Death Pathways

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

A systematic identification of anti-inflammatory active components derived from Mu Dan Pi and their applications in inflammatory bowel disease

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