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Imatinib disturbs lysosomal function and morphology and impairs the activity of mTORC1 in human hepatocyte cell lines

Food Chem Toxicol. 2022-02; 
No?mi Johanna Roos, Riccardo Vincenzo Mancuso, Gerda Mawududzi Sanvee, Jamal Bouitbir, Stephan Kr?henbühl
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Proteins, Expression, Isolation and Analysis … on a 0.2 μm nitrocellulose membrane (Bio-Rad, 1620112) using the eBlot L1 transfer sandwich (GenScript, L00724) and wet protein transfer system (GenScript, Piscataway, NJ, USA)?… Get A Quote

摘要

The tyrosine kinase inhibitors (TKIs) imatinib and lapatinib are associated with severe hepatotoxicity, whose mechanisms are currently under investigation. As amphiphilic drugs, imatinib and lapatinib enrich in lysosomes. In the present study, we investigated their effects on lysosomal morphology and function in HepG2 and HuH-7?cells and explored possible links between lysosomal dysfunction and hepatotoxicity. Both TKIs increased the lysosomal volume time and concentration-dependently in HepG2 and HuH-7?cells. In HepG2 cells, lapatinib and imatinib raised the lysosomal pH and destabilized the lysosomal membrane, thereby impairing lysosomal proteolytic activity such as cathepsin B processing. Imatinib activate... More

關鍵詞

Autophagy, HepG2 cells, Hepatotoxicity, TFEB, Tyrosine kinase inhibitors (TKI), mTORC1
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