Integrated Proteomics and Metabolomics Reveal the Mechanism of Nephrotoxicity Induced by Triptolide.
Chem Res Toxicol
; 33(7): 1897-1906, 2020 07 20.
Article
en En
| MEDLINE
| ID: mdl-32519852
Triptolide (TP), the main active ingredient of Tripterygium wilfordii Hook F., has great potential in the treatment of autoimmune diseases. However, it has been found that the side effects of TP involve multiple organs and systems, of which the most serious side effects relate to the kidney. The mechanism of nephrotoxicity caused by TP requires further investigation. In the present study, we integrated proteomic and metabolomic methods to identify proteins and small molecule metabolites associated with TP-induced nephrotoxicity. There was a significant difference (p value <0.05) in the expression changes of 357 proteins for quantitative proteomics. In addition, high resolution metabolomic data showed significant changes in the levels of 9 metabolites, including hypoxanthine, PC(22:0/18:4), sphingosine, phenylalanine, etc. Finally, based on the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database for network analysis, it was determined that the 7 differentially expressed proteins were highly correlated with these 9 metabolites. Enrichment analysis revealed that the metabolic pathways involved purine and pyrimidine metabolism, glycerol and phospholipid metabolism, sphingolipid metabolism, and amino acid metabolism. The key target proteins were verified by Western blot technology, and the mechanism of TP-induced nephrotoxicity was further elucidated to provide a basis for safe and rational application.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenantrenos
/
Diterpenos
/
Riñón
/
Enfermedades Renales
Límite:
Animals
Idioma:
En
Revista:
Chem Res Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China