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.

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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.

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Study IDST002379
Study TitleGlucose flux analysis of NLRP3 inflammasome activated macrophages
Study TypeBasic research
Study SummaryActivating 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 NameZhu
First NameXuewei
Address575 Patterson Ave, Winston-Salem, NC 27101
Emailxwzhu@wakehealth.edu
Phone3367131445
Submit Date2022-11-15
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-12-15
Release Version1
Xuewei Zhu Xuewei Zhu
https://dx.doi.org/10.21228/M8Q13W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN003877 AN003878
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Dionex Ultimate 3000 Thermo Dionex Ultimate 3000
Column Waters XBridge Amide (100 x 4.6mm,3.5um) Waters XBridge Amide (100 x 4.6mm,3.5um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Plus Orbitrap Thermo Q Exactive Plus Orbitrap
Ion Mode POSITIVE NEGATIVE
Units Fractional enrichment Fractional enrichment

MS:

MS ID:MS003618
Analysis ID:AN003877
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:For each sample, 3 µL solution was injected into the LC-MS for analysis. The HPLC analysis of the isotope-labeled samples was performed using Ultimate 3000 UHPLC (Dionex) as described (Duan et al., 2022). The mass spectrometry analysis was performed using Q Exactive Plus mass spectrometer (Thermo Fisher Scientific). The mass spectrometers were equipped with a HESI probe and operated in the positive/negative switching mode. When Q Exactive Plus mass spectrometer was used, the relevant parameters were as listed: heater temperature, 120 °C; sheath gas, 30; auxiliary gas, 10; sweep gas, 3; spray voltage, 3.0 kV; capillary temperature, 320°C; S-lens, 55. The resolution was set at 70,000 (at m/z 200). Maximum injection time (max IT) was set at 200 ms and automated gain control (AGC) was set at 3 × 106. The LC-MS peak extraction and integration of the raw data were performed using commercially available software Sieve 2.0 (Thermo Fisher Scientific). The integrated peak area was used to calculate 13C enrichment. Natural abundance correction was performed using software R with Bioconductor R package IsoCorrectoR.
Ion Mode:POSITIVE
  
MS ID:MS003619
Analysis ID:AN003878
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:For each sample, 3 µL solution was injected into the LC-MS for analysis. The HPLC analysis of the isotope-labeled samples was performed using Ultimate 3000 UHPLC (Dionex) as described (Duan et al., 2022). The mass spectrometry analysis was performed using Q Exactive Plus mass spectrometer (Thermo Fisher Scientific). The mass spectrometers were equipped with a HESI probe and operated in the positive/negative switching mode. When Q Exactive Plus mass spectrometer was used, the relevant parameters were as listed: heater temperature, 120 °C; sheath gas, 30; auxiliary gas, 10; sweep gas, 3; spray voltage, 3.0 kV; capillary temperature, 320°C; S-lens, 55. The resolution was set at 70,000 (at m/z 200). Maximum injection time (max IT) was set at 200 ms and automated gain control (AGC) was set at 3 × 106. The LC-MS peak extraction and integration of the raw data were performed using commercially available software Sieve 2.0 (Thermo Fisher Scientific). The integrated peak area was used to calculate 13C enrichment. Natural abundance correction was performed using software R with Bioconductor R package IsoCorrectoR.
Ion Mode:NEGATIVE
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