Summary of Study ST002379

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 IDST002379
Study TitleGlucose flux analysis of NLRP3 inflammasome activated macrophages
Study TypeBasic research
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 Date2022-11-15
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
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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Treatment:

Treatment ID:TR002480
Treatment Summary:LPS-primed BMDMs were stimulated with or without 5 mM ATP in the presence or absence of 10 uM JX06 for 30 min. 13C tracing started by replacing medium with glucose-free medium supplemented with 2.06 g/L [U-13C]-glucose (Cayman Chemical) for 90 min.
Treatment:in vitro cell culture treatment
Treatment Compound:LPS, ATP, JX06
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