Uptake of ferritin by isolated rat hepatocytes. Effect of metabolic inhibitors and iron.

To further characterize the hepatic endocytic pathway of ferritin, the effects of inhibitors of intracellular dissociation of ligands (monensin 15 microM, chloroquine 400 microM), intracellular proteolysis (leupeptin 100 microM) and iron loading on the endocytosis of 125I-rat liver ferritin were studied in isolated rat hepatocytes. Cell associated radioactivity at 37 degrees C was decreased by 27% with chloroquine and 18% with monensin after 4 h. Cell associated radioactivity increased by 38% with leupeptin at 37 degrees C. Acid soluble radioactivity in the extracellular medium was significantly decreased at 4 h in the leupeptin group, which suggests that leupeptin inhibited the lysosomal degradation of the 125I-ferritin resulting in intracellular accumulation of ligand rather than increased uptake of ferritin. Iron loading of cells (5.4-fold increase in intracellular iron) did not significantly alter the binding or accumulation of 125I-ferritin. The characteristics of the endocytic pathway for ferritin are more similar to the asialoglycoprotein receptor than the transferrin receptor, and the hepatic uptake of ferritin is unaffected in this study by increasing the intracellular iron concentration.