Expression of haptoglobin receptors in human hepatoma cells.

Abstract

The uptake of radio-labeled hemoglobin-haptoglobin complex (Hb-Hp) by human hepatoma PLC/PRF/5 and HepG2 cells was investigated in an attempt to characterize the uptake process and intracellular transport. Human hepatoma cells took up Hb-Hp in a receptor-mediated manner. Scatchard analysis of binding revealed that PLC/PRF/5 and HepG2 cells exhibited about 21,000 and 63,000 haptoglobin receptors/cell, with a dissociation constant (Kd) of 8.0 and 17 nM, respectively. Human hepatocytes in primary culture also expressed about 84,000 receptors/cells, with a Kd of 7.4 nM. The hemoglobin-haptoglobin complex was internalized and subsequently the internalized Hb-Hp was slowly degraded in the cells. Preincubation of the cells with Hb-Hp resulted in a decrease in binding of the radioactive Hb-Hp to the cell surface, and was accompanied with an accumulation of intracellular receptors. The uptake of Hb-Hp by the cells was not inhibited by 100 microM chloroquine or by 10 mM methylamine, but was inhibited by 50 microM monodansylcadaverine. Hemoglobin-heme taken up by the cells induced microsomal heme oxygenase. Thus, human hepatoma PLC/PRF/5 and HepG2 cells can take up Hb-Hp by haptoglobin receptor-mediated endocytosis and Hb-Hp probably causes translocation of the haptoglobin receptors from the cell surface to the cell interior where they can be degraded. The internalized heme-moiety of hemoglobin can regulate the expression of heme oxygenase.

• Authors: M Okuda, R Tokunaga, S Taketani
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1136 Issue 2 Pg. 143-9 (Aug 12 1992) ISSN: 0006-3002 [Print] Netherlands
• PMID: 1354488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Haptoglobins
• Hemoglobins
• Methylamines
• Receptors, Cell Surface
• haptoglobin-hemoglobin complex
• Chloroquine
• methylamine
• Heme Oxygenase (Decyclizing)
• Transglutaminases
• monodansylcadaverine
• Cadaverine

Topics

• Biological Transport
• Cadaverine (analogs & derivatives, pharmacology)
• Carcinoma, Hepatocellular (metabolism)
• Cells, Cultured
• Chloroquine (pharmacology)
• Endocytosis
• Enzyme Induction
• Haptoglobins (metabolism)
• Heme Oxygenase (Decyclizing) (metabolism)
• Hemoglobins (metabolism)
• Humans
• Immunoblotting
• Kinetics
• Liver (cytology, metabolism)
• Liver Neoplasms (metabolism)
• Methylamines (pharmacology)
• Microsomes, Liver (enzymology)
• Receptors, Cell Surface (metabolism)
• Transglutaminases (antagonists & inhibitors)
• Tumor Cells, Cultured