Inhibition of nerve growth factor‐stimulated neurite outgrowth by methylamine‐modified α2‐macroglobulin

P. H. Koo, D. J. Liebl

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

α2-Macroglobulin (α2M) is a rather ubiquitous protein in extracellular spaces of mammals. It is an inhibitor of endopeptidases, can be modified by aliphatic amines, and combines with a number of hormones/cytokines such as β-nerve growth factor (NGF) [Koo PH, Stach RW (1989): J Neurosci Res 22:247]. The objective of this study is to compare the NGF-binding properties of methylamine-modified human α2M (MA-α2M) versus normal α2M and their effects on the biological activity of NGF and neurite extension by embryonic chicken dorsal root ganglia. As determined by gel filtration, polyacrylamide gel electrophoresis, and equilibrium binding studies, these two forms of α2M are similar in their binding affinities, with MA-α2M binding about twice as much NGF as normal α2M. Both normal α2M and MA-α2M combine noncovalently with NGF, and prior modification of α2M is unnecessary for the binding to occur. In contrast to normal α2M, MA-α2M potently inhibits the biological activity of NGF and exerts a dose-dependent inhibition on the NGF-stimulated neurite outgrowth by embryonic chicken dorsal root ganglia in culture. The inhibitory effect of MA-α2M can be overcome by higher NGF concentrations, but is irreversible at lower NGF concentrations. Trypsin- modified α2M combines covalently and noncovalently with more NGF than normal α2M but has very little neurite inhibitory activity. The mechanism of inhibition by MA-α2M is discussed.

Original languageEnglish (US)
Pages (from-to)678-692
Number of pages15
JournalJournal of Neuroscience Research
Volume31
Issue number4
DOIs
StatePublished - Apr 1992
Externally publishedYes

Keywords

  • binding affinity
  • biogenic amine
  • cytokine
  • neurotransmitter
  • proteinase inhibitor

ASJC Scopus subject areas

  • Neuroscience(all)

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