S. Hashida, E. Kominami, N. Katunuma
Apr 1, 1982
Citations
1
Influential Citations
40
Citations
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Journal
Journal of biochemistry
Abstract
E-64 is a specific thiol proteinase inhibitor which inhibits lysosomal cathepsins B and L in vitro and in vivo [Hashida, S., Towatari, T., Kominami, E., & Katunuma, N. (1980) J. Biochem. 88, 1805-1811]. This work showed and that E-64 administered in vivo penetrates into lysosomes of the liver, possibly by permeation rather than by endocytosis. When [3H]E-64 was injected into rats i.p., high radioactivity was observed in the serum after a short time and it decreased rapidly. Incorporation of [3H]E-64 into the cytosol fraction of liver also began to decrease 1 h after the injection. Radioactivity in the mitochondrial-lysosomal fraction increased to a maximum after 6 h and then gradually decreased until 72 h. Dose-dependent incorporation of [3H]E-64 into the serum and liver cytosol was observed at all doses tested, but that into the lysosomal fraction increased linearly with doses of only up to 0.l5 mg/100 body weight of E-64. E-64 in the serum and liver cytosol was mostly present in the free form, whereas that in the lysosomal fraction was mostly protein-bound. The time course and dose-response of lysosomal cathepsin B activity to E-64 were closely related to the radioactivity in the protein-bound fraction of the lysosomes. These results suggest that E-64 was transported to the liver cytosol in the free form in the blood and permeated into the lysosomes, where it bound to, and inactivated, E-64 sensitive proteinases.