Summary of Study ST002371

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.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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 IDST002371
Study TitleHigh-resolution metabolomics analysis of NLRP3 inflammasome activated 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 Pattern Ave.
Emailxwzhu@wakehealth.edu
Phone3367131445
Submit Date2022-11-15
Num Groups3
Total Subjects12
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailGC-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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Collection:

Collection ID:CO002453
Collection Summary:Mouse bone marrow was cultured in low glucose DMEM supplemented with 30% L929 cell-conditioned medium, 20% FBS, 2 mM L-glutamine, 1 mM sodium pyruvate, 100 U/ml penicillin, and 100 µg/ml streptomycin for 6-7 days until the cells reached confluence. BMDMs were then reseeded in culture dishes overnight in RPMI-1640 medium containing 1% Nutridoma-SP medium (Sigma-Aldrich). LPS-primed BMDMs were stimulated with 5 mM ATP in the presence or absence of 10 uM JX06 for 45 min. Unstimulated macrophages were used as control.
Sample Type:Macrophages
Storage Conditions:-80℃
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