Summary of project PR001524

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

Project ID: PR001524
Project DOI:doi: 10.21228/M8Q13W
Project Title:Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation
Project Type:Basic research
Project 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
Email:xwzhu@wakehealth.edu
Phone:3367131445

Summary of all studies in project PR001524

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : Contains raw data)
ST002371 High-resolution metabolomics analysis of NLRP3 inflammasome activated macrophages Mus musculus Wake Forest School of Medicine MS 2022-12-15 1 12 Uploaded data (633.1M)*
ST002378 Targeted metabolomics analysis of WT and GSDMDKO macrophages Mus musculus Wake Forest School of Medicine MS 2022-12-15 1 32 Uploaded data (37.1M)*
ST002379 Glucose flux analysis of NLRP3 inflammasome activated macrophages Mus musculus Wake Forest School of Medicine MS 2022-12-15 1 12 Uploaded data (666.3M)*
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