Inhibition of endosome fusion in primary hepatocytes prevents asialoglycoprotein degradation but not uptake of transferrin iron demonstrating that intracellular iron release occurs from early endosomes.
A comparison of the effects of inhibitors of membrane fusion on the uptake of asialoglycoprotein and transferrin by primary rat hepatocytes was made. This showed that while high potassium medium inhibited the degradation but not the uptake of asialoorosomucoid, both transferrin endocytosis and iron delivery to the cells were unaffected. This difference between the two pathways was also observed with an inhibitor of phospholipase A2, bromophenacyl bromide. With the latter, it was found that the asialoglycoproteins failed to traverse from a low-density to a high-density intracellular compartment, implying a role for phospholipase A2 in the trafficking of asialoglycoprotein receptor but not that for transferrin or iron. This demonstrates that, after its release from transferrin, iron is transported to the cytoplasm directly from the early endosome without the need for fusion of the iron-containing vesicle with a lysosome.
Young
S P
SP
Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Edgbaston, Birmingham, UK. s.p.young@bham.ac.uk
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001212:Asialoglycoproteins / Q000378:metabolism*; D001693:Biological Transport, Active; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008561:Membrane Fusion / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014168:Transferrin / Q000378:metabolism*
D000098:Acetophenones; D001212:Asialoglycoproteins; D004791:Enzyme Inhibitors; D014168:Transferrin; D007501:Iron; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide; D011188:Potassium