|show drug details|
|1,4-Naphthalenedione, 5,8-dihydroxy- (9CI)|
|Ki: ||Kd:||Ic 50:||Ec50/Ic50:|
Inhibition of cathepsin D prevents free-radical-induced apoptosis in rat cardiomyocytes.. K Ollinger (2000) Archives of biochemistry and biophysics display abstract
Apoptosis was inhibited in rat cardiomyocytes pretreated with the aspartic protease inhibitor pepstatin A and subsequently exposed to naphthazarin (5,8-dihydroxy-1,4-naphthoquinone). Cathepsin D was released from lysosomes to the cytosol upon exposure to naphthazarin, and the enzyme activity decreased simultaneously. Later, cathepsin D reappeared in granules of increased size, and enzyme activity was restored. Activation of caspase-3-like proteases was detected, and the number of cells showing apoptotic morphology increased with time. Pepstatin A pretreatment did not prevent release of cathepsin D from lysosomes but did significantly inhibit subsequent naphthazarin-induced caspase activation and apoptotic morphology. This suggests that cathepsin D exerts its apoptosis-stimulating effect upstream of caspase-3-like activation.