Summary of Study ST002378

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 PR001524. The data can be accessed directly via it's Project DOI: 10.21228/M8Q13W This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002378
Study TitleTargeted metabolomics analysis of WT and GSDMDKO macrophages
Study TypeMS analysis
Study SummaryActivating macrophage NLRP3 inflammasome can promote excessive inflammation, with severe cell and tissue damage and organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenuates NLRP3 inflammasome activation in murine and human macrophages and septic mice by lowering caspase-1 cleavage and IL-1beta secretion. Inhibiting PDHK reverses NLRP3 inflammasome-induced metabolic reprogramming, enhances autophagy, promotes mitochondrial fusion over fission, preserves cristae ultrastructure, and attenuates mitochondrial ROS production. The suppressive effect of PDHK inhibition on the NLRP3 inflammasome is independent of its canonical role as a pyruvate dehydrogenase regulator. We suggest that PDHK inhibition improves mitochondrial fitness by reversing NLRP3 inflammasome activation in acutely inflamed macrophages.
Institute
Wake Forest School of Medicine
Last NameZhu
First NameXuewei
Address575 Patterson Ave, Winston-Salem, NC 27101
Emailxwzhu@wakehealth.edu
Phone3367131445
Submit Date2022-11-16
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2022-12-15
Release Version1
Xuewei Zhu Xuewei Zhu
https://dx.doi.org/10.21228/M8Q13W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN003875 AN003876
Analysis type MS MS
Chromatography type Ion pair Unspecified
Chromatography system Shimadzu Nexera X2 Shimadzu Nexera X2
Column Agilent Zorbax Eclipse Plus C18 (100 x 2.1mm, 1.8 um) Restek Ultra PFPP (150 x 2.1mm,3um)
MS Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name Shimadzu Nexera X2 Shimadzu Nexera X2
Ion Mode NEGATIVE NEGATIVE
Units Peak area ratio Peak area ratio

MS:

MS ID:MS003616
Analysis ID:AN003875
Instrument Name:Shimadzu Nexera X2
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The analysis was performed on a Shimadzu Nexera UHPLC system coupled with a Shimadzu LCMS-8050 triple-quadrupole mass spectrometer (Kyoto, Japan). Two LC-MS/MS methods were employed to measure the targets.
Ion Mode:NEGATIVE
  
MS ID:MS003617
Analysis ID:AN003876
Instrument Name:Shimadzu Nexera X2
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:The analysis was performed on a Shimadzu Nexera UHPLC system coupled with a Shimadzu LCMS-8050 triple-quadrupole mass spectrometer (Kyoto, Japan). Two LC-MS/MS methods were employed to measure the targets.
Ion Mode:NEGATIVE
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