Summary of Study ST002774

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 PR001731. The data can be accessed directly via it's Project DOI: 10.21228/M8ZD8R 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 IDST002774
Study TitleMetabolomics studies on L4-5 Dorsal Root Ganglia of Ctrl and cKO mice
Study SummaryMetabolomics studies on Dorsal Root Ganglia (DRGs) (Ctrl and cKO).The specific knockout of PP2Cm in the DRG was achieved by intracellular injection of AAV9-Pirt-Cre (1.0×1013 vg/ml) or AAV9-Pirt (1.0×1013 vg/ml)) as control. Mice were used for experiments at 4 weeks after the injection.
Institute
West China Hospital of Sichuan University
Last NameLi
First NameTao
AddressNo. 37 Guoxue Road, Wuhou District, Chendu 610041, Sichuan, China
Email563234879@qq.com
Phone+8628-85164154
Submit Date2023-07-07
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-09-14
Release Version1
Tao Li Tao Li
https://dx.doi.org/10.21228/M8ZD8R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001731
Project DOI:doi: 10.21228/M8ZD8R
Project Title:Defective Branched-Chain Amino Acid Catabolism in Dorsal Root Ganglia Contributes to Mechanical Pain
Project Summary:Impaired branched-chain amino acid (BCAA) catabolism has recently been implicated in the development of mechanical pain, but the molecular mechanisms are unclear. Here we report that defective BCAA catabolism in dorsal root ganglia (DRG) neurons sensitizes mice to mechanical pain by increasing lactate production and Piezo2 expression, a mechanotransduction channel. In high-fat diet fed obese mice, we observed a downregulation of PP2Cm, a key regulator in BCAA catabolic pathway, in DRG neurons. Mice with conditional knockout of PP2Cm in DRG neurons (cKO) exhibited mechanical allodynia under normal or spare nerve injury (SNI)-induced neuropathic injury conditions. Further, in patients with peripheral neuropathic pain, we found that the Visual Analogue Scale (VAS) scores were positively correlated with BCAA contents in plasma, highlighting a link between peripheral neuropathic pain and dysregulated BCAA catabolism. Mechanistically, defective BCAA catabolism promotes the production of lactate through glycolysis in DRG neurons, which increases H3K18la modification and drives Piezo2 expression. Inhibition of lactate production or silencing of Piezo2 expression attenuated the pain phenotype of cKO to mechanical stimuli. Therefore, our study demonstrates a casual role of defective BCAA catabolism in mechanical pain by enhancing metabolite-mediated epigenetic regulation.
Institute:West China Hospital of Sichuan University
Laboratory:Laboratory of Mitochondria and Metabolism
Last Name:Li
First Name:Tao
Address:No. 37 Guoxue Road, Wuhou District, Chendu 610041, Sichuan, China
Email:563234879@qq.com
Phone:+8628-85164154

Subject:

Subject ID:SU002881
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype
SA295622cKO6cKO
SA295623cKO5cKO
SA295624cKO1cKO
SA295625cKO2cKO
SA295626cKO3cKO
SA295627cKO4cKO
SA295616Ctrl1Ctrl
SA295617Ctrl6Ctrl
SA295618Ctrl5Ctrl
SA295619Ctrl2Ctrl
SA295620Ctrl3Ctrl
SA295621Ctrl4Ctrl
Showing results 1 to 12 of 12

Collection:

Collection ID:CO002874
Collection Summary:Mice were anaesthetized with volatile anesthetic isoflurane (3-4% for induction, 1-2% for maintenance, in O2≈ 2 L/min). DRG (left L4–L5) were surgically exposed and diessected. Fresh DRG samples were frozen in liquid nitrogen.5-6 DRGs were collected as one sample
Sample Type:DRG

Treatment:

Treatment ID:TR002890
Treatment Summary:No treatment.

Sample Preparation:

Sampleprep ID:SP002887
Sampleprep Summary:Fresh tissue samples were frozen in liquid nitrogen. After thawing on ice, 10 mg tissue was homogenized in -80°C precooled labeled-solution (MeOH: H2O=4:1, v/v) for 30 s, 4 cycles, and placed at -80°C for 30 minutes. In ice water bath, ultrasonic wave was used for 10 min and centrifuged at 14000 rpm. The precipitated protein was dissolved in no labeled-liquid (MeOH: H2O=4:1), vortexed and centrifuged. After derivatization with N-methyl-N-(trimethylsilyl)tri-fluoroacetamide for 30 min, the supernatant was detected by GC-MS. Metabolites were identified by means of KEGG Metabolic pathways.

Combined analysis:

Analysis ID AN004515 AN004516
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Nexera UHPLC LC-30A  Nexera UHPLC LC-30A 
Column Waters BEH Amide (2.1 X 100mm, 1.7μm) Waters BEH Amide (2.1 X 100mm, 1.7μm)
MS Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name Nexera UHPLC LC-30A  Nexera UHPLC LC-30A 
Ion Mode POSITIVE NEGATIVE
Units pmoles/l pmoles/l

Chromatography:

Chromatography ID:CH003392
Instrument Name:Nexera UHPLC LC-30A 
Column Name:Waters BEH Amide (2.1 X 100mm, 1.7μm)
Column Temperature:40℃
Flow Gradient:0～1.5min,90%B.1.5~5min,90-45%B.5~10min,45%B.10~11min,45~90B.11~23min,90B
Flow Rate:0.3ml/min
Solvent A:10% acetonitrile/90% water; 0.2% acetic acid
Solvent B:90% acetonitrile/10% water; 0.2% acetic acic
Chromatography Type:HILIC

MS:

MS ID:MS004262
Analysis ID:AN004515
Instrument Name:Nexera UHPLC LC-30A 
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:-
Ion Mode:POSITIVE
  
MS ID:MS004263
Analysis ID:AN004516
Instrument Name:Nexera UHPLC LC-30A 
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:-
Ion Mode:NEGATIVE
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