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.

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Study IDST000174
Study TitleMouse macrophages from bone marrow treatment
Study TypeGlycolysis/TCA/Nucleotide analysis (tissue/cells)
Study SummaryThe 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
DepartmentBiomedical Research Core Facilities
LaboratoryMetabolomics core
Last NameKachman
First NameMaureen
Address6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Email mkachman@umich.edu
Submit Date2015-06-05
Num Groups10
Total Subjects14
Raw Data AvailableYes
Raw Data File Type(s)d
Uploaded File Size4.4 G
Analysis Type DetailLC-MS
Release Date2015-12-28
Release Version1
Maureen Kachman Maureen Kachman
https://dx.doi.org/10.21228/M8FS30
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR000151
Project DOI:doi: 10.21228/M8FS30
Project Title:Nlrp3
Project Summary:Unstimulated vs Stimulated n=4
Institute:University of Michigan
Department:Pathology
Laboratory:Nunez
Last Name:Nunez
First Name:Gabriel
Address:Ann Arbor, MI
Email:bclx@med.umich.edu
Phone:734-764-8514

Subject:

Subject ID:SU000193
Subject Type:Animal
Subject Species:Mus musculus
Taxonomy ID:10090
Species Group:Mammals

Factors:

Subject type: Animal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Agonist Priming Rinse
SA009449S00014354CL097 LPS None
SA009450S00014355CL097 LPS None
SA009451S00014356Gardiquimod LPS None
SA009452S00014357Gardiquimod LPS None
SA009453S00014352Gramicidin LPS H2O rinse
SA009454S00014350Gramicidin LPS None
SA009455S00014348Gramicidin None None
SA009456S00014353Gramidicin LPS H2O rinse
SA009457S00014351Gramidicin LPS None
SA009458S00014349Gramidicin None None
SA009459S00014346None LPS None
SA009460S00014347None LPS None
SA009461S00014345None None None
SA009462S00014344None None None
Showing results 1 to 14 of 14

Collection:

Collection ID:CO000180
Collection Summary:-
Sample Type:Cells

Treatment:

Treatment ID:TR000200

Sample Preparation:

Sampleprep ID:SP000194
Sampleprep Summary:-
Sampleprep Protocol Filename:Gly-TCA-nucleotides_analysis_protocol-2015-03-09.docx

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

Analysis:

Analysis ID:AN000268
Laboratory Name:MRC2 (University of Michigan)
Analysis Type:MS
Acquisition ID:AQM020
Acquisition Parameters File:QTOF-002-HILIC-35min-1mm-No_Insert.m.zip
Instrument Name:Agilent 6530 QTOF
Processing Parameters File:EX00289-MassHunterQuant-GlyTCA-LCMS-DataAnalysis-Method.m.zip
Chromatography ID:CH000191
Num Factors:10
Num Metabolites:18
Units:pmol/mg protein
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