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.
Study ID | ST002379 |
Study Title | Glucose flux analysis of NLRP3 inflammasome activated macrophages |
Study Type | Basic research |
Study Summary | Activating 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 Name | Zhu |
First Name | Xuewei |
Address | 575 Patterson Ave, Winston-Salem, NC 27101 |
xwzhu@wakehealth.edu | |
Phone | 3367131445 |
Submit Date | 2022-11-15 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2022-12-15 |
Release Version | 1 |
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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 |