Summary of Study ST002378
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 | ST002378 |
| Study Title | Targeted metabolomics analysis of WT and GSDMDKO macrophages |
| Study Type | MS analysis |
| 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 | 2022-11-16 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-12-15 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO002460 |
| Collection Summary: | Macrophages were lysed, and polar metabolites were extracted using methanol and H2O (80:20; HPLC Grade; Sigma-Aldrich). Briefly, After treatment, immediately aspirate medium at room temperature. Immediately place the plate on dry ice, and add 1 mL 80% methanol/water (both HPLC grade) (pre-cooled in -80oC for at least 1hr).Remove the plate from -80oC freezer and put it on dry ice, scrape cells into extraction solvent. Transfer the whole cell extract to a new Eppendorf tube placed on ice. Centrifuge at 20 000 rcf for 10 min, 4oC.Transfer the supernatant into two tubes and dry with a speed vacuum at room temperature. |
| Sample Type: | Macrophages |
| Storage Conditions: | Described in summary |
