Tenofovir and adefovir down-regulate mitochondrial chaperone TRAP1 and succinate dehydrogenase subunit B to metabolically reprogram glucose metabolism and induce nephrotoxicity.

ABSTRACT: Despite the therapeutic success of tenofovir (TFV) for treatment of HIV-1 infection, numerous cases of nephrotoxicity have been reported. Mitochondrial toxicity has been purported as the major target of TFV-associated renal tubulopathy but the underlying molecular mechanism remains unclear. In this report, we use metabolomics and proteomics with HK-2 cells and animal models to dissect the molecular pathways underlying nephropathy caused by TFV and its more toxic analog, adefovir (ADV). Proteomic analysis shows that mitochondrial chaperone TRAP1 and mtDNA replicating protein SSBP1 were significantly down-regulated in TFV and ADV treated HK-2 cells compared with controls. Transmission electron microscopy (TEM) revealed that TFV and ADV-treated HK-2 cells had accumulated glycogen, a phenotype

SUBMITTER: Zhao X 

PROVIDER: S-EPMC5387747 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature