Summary of project PR001731
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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| 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 |
Summary of all studies in project PR001731
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002774 | Metabolomics studies on L4-5 Dorsal Root Ganglia of Ctrl and cKO mice | Mus musculus | West China Hospital of Sichuan University | MS | 2023-09-14 | 1 | 12 | Uploaded data (3.6M)* |
