Nickel is a specific antagonist for the catabolism of activated α2-macroglobulin

Ravi K. Kancha, M. Mahmood Hussain*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The multifunctional low density lipoprotein receptor-related protein/α2-macroglobulin receptor (LRP) binds and degrades several ligands involved in protease and lipoprotein metabolism. We previously reported that nickel (Ni2+) specifically inhibits the binding of activated α2-macroglobulin (α2M*) at 4°C to LRP and had no effect on the binding of other ligands to the receptor (Hussain et al. (1995) Biochem. 34, 16074-16081). In the current investigation, we have examined the effect of Ni2+ on the catabolism of 125I-labeled α2M*, receptor-associated protein (RAP) and lactoferrin at physiologic temperatures by fibroblasts. Nickel completely inhibited the degradation of α2M* over a wide range of concentrations (0.3-2.4 nM); 50% inhibition for the degradation of 1.2 nM α2M* was observed at 0.5 mM Ni2+. Furthermore, nickel inhibited the binding, internalization and degradation of 125I-α2M* in a dose- and time-dependent manner. In contrast, the degradation of several concentrations of 125I-RAP by fibroblasts was not affected by different amounts of Ni2+ for various times. Similarly, Ni2+ did not inhibit the degradation of lactoferrin either before or after treating the cells with heparitinase to remove cell-surface proteoglycans. The degradation of lactoferrin was, however, inhibited by the RAP indicating that lactoferrin degradation was mediated by the LRP. These data suggest that Ni2+ is a specific inhibitor for the degradation of α2M*.

Original languageEnglish
Pages (from-to)231-240
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1355
Issue number3
DOIs
Publication statusPublished - 1 Mar 1997
Externally publishedYes

Keywords

  • α-Macroglobulin
  • Catabolism
  • Lactoferrin
  • LDL receptor-related protein
  • Lipoprotein receptor-related protein
  • Nickel
  • Receptor
  • Receptor associated protein

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