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:
Combined analysis:
Analysis ID | AN000268 |
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Analysis type | MS |
Chromatography type | HILIC |
Chromatography system | Agilent 1260 |
Column | Phenomenex Luna NH2 (150 x 1mm,3um) |
MS Type | ESI |
MS instrument type | QTOF |
MS instrument name | Agilent 6530 QTOF |
Ion Mode | NEGATIVE |
Units | pmol/mg protein |
Chromatography:
Chromatography ID: | CH000191 |
Methods ID: | AQM020 |
Methods Filename: | QTOF-002-HILIC-35min-1mm-No_Insert.m.zip |
Instrument Name: | Agilent 1260 |
Column Name: | Phenomenex Luna NH2 (150 x 1mm,3um) |
Chromatography Type: | HILIC |