Endocytosis of lactate dehydrogenase isoenzyme M4 in rats in vivo. Experiments with enzyme labelled with O-(4-diazo-3,5-di[125I]iodobenzoyl)sucrose.
1. Pig lactate dehydrogenase isoenzyme M4 was labelled with O-(4-diazo-3,5-di[125I]iodobenzoyl)sucrose and injected intravenously into rats. Previous work has shown that this label does not influence the clearance of the enzyme (half-life about 26 min) and that it is retained within the lysosomes for several hours after endocytosis and breakdown of the protein [De Jong, Bouma & Gruber (1981) Biochem. J. 198, 45--51]. 2. The distribution of the radioactivity over a large number of tissues was determined 2 h after injection. A high percentage of the injected dose was found in liver (41%), spleen (10%) and bone including marrow (21%). 3. Autoradiography indicated uptake of the enzyme mainly by Kupffer cells of the liver, by spleen macrophages and by bone marrow macrophages. 4. Liver cells were isolated 1 h after injection of the enzyme. Kupffer cells, endothelial cells and parenchymal cells were found to endocytose the enzyme at rates corresponding to 4230, 35 and 25 ml of plasma/day per g of cell protein, respectively. 5. Previous injection of carbon particles greatly reduced the uptake of the enzyme by liver and spleen, but the uptake by bone marrow was not significantly changed.
D000818:Animals; D001345:Autoradiography; D001853:Bone Marrow / Q000201:enzymology; D002244:Carbon / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D006207:Half-Life; D007463:Iodobenzoates; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D007463:Iodobenzoates; D007527:Isoenzymes; D002244:Carbon; C033177:O-(4-diazo-3,5-diiodobenzoyl)sucrose; D007770:L-Lactate Dehydrogenase