Dissection of Targeting Molecular Mechanisms of Aristolochic Acid-induced Nephrotoxicity via a Combined Deconvolution Strategy of Chemoproteomics and Metabolomics.

ABSTRACT: Aristolochic acid (AA), mainly derived from herbal Aristolochia and Asarum plants, was listed as a human carcinogen class I in 2002. Aristolochic acid nephropathy (AAN) is a rapidly progressive tubulointerstitial nephritis and urothelial cancer caused by AA. However, the targeting molecular mechanisms of AAs-induced nephrotoxicity are largely unclear. This study aims to dissect targeting molecular mechanisms of AA-induced nephrotoxicity. Activity-based protein profiling (ABPP) in combination with cellular thermal shift assay (CETSA) was performed to identify the AAs binding target proteins. Our data indicated that several key enzymes in the metabolic process and mitochondrial respiration including IDH2 and MDH2 (Krebs cycle), PKM and LDH (aerobic respiration), FASN (fatty aci

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC8935225 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature