Summary of Study ST002371
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 | ST002371 |
| Study Title | High-resolution metabolomics analysis of NLRP3 inflammasome activated 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 Pattern Ave. |
| xwzhu@wakehealth.edu | |
| Phone | 3367131445 |
| Submit Date | 2022-11-15 |
| Num Groups | 3 |
| Total Subjects | 12 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | GC-MS |
| Release Date | 2022-12-15 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003866 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Thermo Dionex Ultimate 3000 |
| Column | Waters XBridge Amide (100 x 4.6mm,3.5um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive Plus Orbitrap |
| Ion Mode | UNSPECIFIED |
| Units | peak area |
Chromatography:
| Chromatography ID: | CH002864 |
| Chromatography Summary: | The HPLC (Ultimate 3000 UHPLC) is coupled to QE-MS (Thermo Scientific) for metabolite separation and detection. An Xbridge amide column (100 × 2.1 mm i.d., 3.5 μm; Waters) is employed for compound separation at room temperature. The mobile phase A is water containing 5 mM ammonium acetate (pH 6.8), and the mobile phase B is acetonitrile. The linear gradient used is as follows: 0 min, 85% B; 1.5 min, 85% B, 5.5 min, 35% B; 10 min, 35% B, 10.5 min, 35% B, 14.5 min, 35% B, 15 min, 85% B, and 20 min, 85% B. The flow rate was 0.15 mL/min from 0 to 10 min and 15 to 20 min and 0.3 mL/min from 10.5 to 14.5 min. The QE-MS is equipped with a HESI probe with related parameters set as below: heater temperature, 120 °C; sheath gas, 30; auxiliary gas, 10; sweep gas, 3; spray voltage, 3.0 kV for the positive mode and 2.5 kV for the negative mode; capillary temperature, 320 °C; S-lens, 55; scan range (m/z): 70 to 900 for pos mode (1.31 to 12.5 min) and neg mode (1.31 to 6.6 min) and 100 to 1000 for neg mode (6.61 to 12.5 min); resolution: 70000; automated gain control (AGC), 3 × 106 ions. Customized mass calibration was performed before data acquisition. |
| Methods Filename: | The_HPLC_methods.docx |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Waters XBridge Amide (100 x 4.6mm,3.5um) |
| Flow Gradient: | The linear gradient used is as follows: 0 min, 85% B; 1.5 min, 85% B, 5.5 min, 35% B; 10 min, 35% B, 10.5 min, 35% B, 14.5 min, 35% B, 15 min, 85% B, and 20 min, 85% B. |
| Flow Rate: | 0.15 mL/min from 0 to 10 min and 15 to 20 min and 0.3 mL/min from 10.5 to 14.5 min. |
| Solvent A: | 100% water; 5 mM ammonium acetate, pH 6.8 |
| Solvent B: | 100% acetonitrile |
| Chromatography Type: | HILIC |
