Cellular catabolism of recombinant tissue-type plasminogen activator. Identification and characterization of a novel high affinity uptake system on rat hepatocytes.
The uptake, internalization, and intracellular degradation of 125I-labeled recombinant tissue-type plasminogen activator (rt-PA) by isolated rat hepatocytes was investigated. Incubation at 37 degrees C resulted in internalization of 125I-rt-PA, followed by the appearance of labeled trichloroacetic acid-soluble material in the incubation media due to degradation of rt-PA. Degradation of rt-PA was inhibited by the presence of NH4Cl (10 mM) or chloroquine (1 mM) (lysosomal tropic agents) in the incubation media. This suggests that rt-PA degradation occurs intracellularly, perhaps within the lysosomes. 125I-rt-PA was taken up by rat hepatocytes through a specific, high affinity mechanism with half-maximal uptake at 10 nM. Uptake of 125I-rt-PA was not inhibited by glycopeptides isolated from rt-PA nor by several other glycoproteins known to be cleared by identified hepatic receptors. These results suggest that the uptake of rt-PA by rat hepatocytes involves a receptor specific for t-PA and is not mediated by a carbohydrate-specific receptor.
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D001692:Biological Transport; D010450:Endopeptidases; D060748:Fetuins; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism*; D012697:Serine Endopeptidases; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000378:metabolism
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D060748:Fetuins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; C017029:asialofetuin; D010450:Endopeptidases; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase; D010959:Tissue Plasminogen Activator