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 ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : 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)* |
