Summary of Study ST000174
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000151. The data can be accessed directly via it's Project DOI: 10.21228/M8FS30 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST000174 |
| Study Title | Mouse macrophages from bone marrow treatment |
| Study Type | Glycolysis/TCA/Nucleotide analysis (tissue/cells) |
| Study Summary | The noncanonical inflammasome induced by intracellular lipopolysaccharide (LPS) leads to caspase-11-dependent pyroptosis, which is critical for induction of endotoxic shock in mice. However, the signaling pathway downstream of caspase-11 is unknown. We found that cytosolic LPS stimulation induced caspase-11-dependent cleavage of the pannexin-1 channel followed up by ATP release, which in turn activated the purinergic P2X7 receptor to mediate cytotoxicity. In the absence of P2X7 or pannexin-1, pyroptosis induced by cytosolic LPS was abrogated. Cleavage of pannexin-1 required the catalytic activity of caspase-11 and was essential for ATP release and P2X7-mediated pyroptosis. Priming the caspase-11 pathway in vivo with LPS or Toll-like receptor-3 (TLR3) agonist resulted in high mortality in wild-type mice after secondary LPS challenge, but not in Casp11(-/-), Panx1(-/-), or P2x7(-/-) mice. These results reveal a critical role for pannexin-1 and P2X7 downstream of caspase-11 for pyroptosis and susceptibility to sepsis induced by the noncanonical inflammasome. Research is published, core data not used but project description is relevant: http://www.sciencedirect.com/science/article/pii/S1074761315004094 |
| Institute | University of Michigan |
| Department | Biomedical Research Core Facilities |
| Laboratory | Metabolomics core |
| Last Name | Kachman |
| First Name | Maureen |
| Address | 6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714 |
| mkachman@umich.edu | |
| Submit Date | 2015-06-05 |
| Num Groups | 10 |
| Total Subjects | 14 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Uploaded File Size | 4.4 G |
| Analysis Type Detail | LC-MS |
| Release Date | 2015-12-28 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Subject:
| Subject ID: | SU000193 |
| Subject Type: | Animal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammals |
