sm-164 and Systemic-Inflammatory-Response-Syndrome

sm-164 has been researched along with Systemic-Inflammatory-Response-Syndrome* in 1 studies

Other Studies

1 other study(ies) available for sm-164 and Systemic-Inflammatory-Response-Syndrome

ArticleYear
Zinc finger protein 91 mediates necroptosis by initiating RIPK1-RIPK3-MLKL signal transduction in response to TNF receptor 1 ligation.
    Toxicology letters, 2022, Mar-01, Volume: 356

    Necroptosis is a form of regulated programmed cell death that is mediated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting serine/threonine protein kinase-3 (RIPK3), and mixed lineage kinase domain-like protein (MLKL); however, it is not known whether zinc finger protein 91 (ZFP91) is involved in this process. Here, we investigated ZFP91 as a potential mediator of necroptosis. Our mechanistic study demonstrates that ZFP91 promotes RIPK1-RIPK3 interaction, thereby stabilizing the RIPK1 and RIPK3 proteins and facilitating necroptosis. ZFP91 stabilized RIPK1 to promote cell death by inducing RIPK1 de-ubiquitination. ZFP91 also significantly increased production of mitochondrial reactive oxygen species (ROS). Accumulation of ROS promoted RIPK3-independent necroptosis triggered by tumor necrosis factor (TNF). in vivo, ZFP91 knockdown alleviated TNFα-induced systemic inflammatory response syndrome (SIRS). These results provide direct evidence that ZFP91 plays an important role in the initiation of RIPK1/RIPK3-dependent necroptosis in vitro and in vivo. We discussed the potential of ZFP91 as a novel therapeutic target for necroptosis-associated diseases.

    Topics: Amino Acid Chloromethyl Ketones; Animals; Bridged Bicyclo Compounds, Heterocyclic; Cell Line; Cell Survival; Gene Expression Regulation; Humans; Mice; Protein Kinases; Reactive Oxygen Species; Receptor-Interacting Protein Serine-Threonine Kinases; Receptors, Tumor Necrosis Factor, Type I; Signal Transduction; Systemic Inflammatory Response Syndrome; Triazoles; Tumor Necrosis Factor-alpha; Ubiquitin-Protein Ligases

2022