β-Amyloid (Aβ) causes detachment of N1E-115 neuroblastoma cells by acting as a scaffold for cell-associated plasminogen activation

Onno Kranenburg, Barend Bouma, Yoony Y J Gent, Colinda J. Aarsman, Rakez Kayed, George Posthuma, Bettina Schiks, Emile E. Voest, Martijn F B G Gebbink

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7 Scopus citations

Abstract

A major component of neuritic plaques in brain tissue of Alzheimer's disease patients is the β-amyloid peptide (Aβ). Accumulation of Aβ has been associated with increased neuronal cell death and cognitive decline. We have previously shown that amyloid peptides like Aβ bind tissue-type plasminogen activator (tPA) and stimulate plasmin production. Here we investigated how Aβ regulates plasmin formation by N1E-115 neuroblastoma cells and the effects of Aβ-mediated plasmin formation on cell attachment and cell survival. We find that Aβ induces excessive cell-associated plasmin generation that causes cell detachment. Cell detachment is inhibited by carboxypeptidase B (CPB), an enzyme that blocks plasmin formation by cleaving off C-terminal lysine residues. Plasmin and CPB control Aβ-induced cell detachment independently of direct effects on cell viability. Aβ40 as well as oligomeric and fibrillar forms of Aβ42 stimulated tPA-mediated plasminogen activation and cell detachment. Our results suggest that plasmin-mediated cell detachment could contribute to the pathological effects of Aβ in diseased brain.

Original languageEnglish (US)
Pages (from-to)496-508
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume28
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Kranenburg, O., Bouma, B., Gent, Y. Y. J., Aarsman, C. J., Kayed, R., Posthuma, G., Schiks, B., Voest, E. E., & Gebbink, M. F. B. G. (2005). β-Amyloid (Aβ) causes detachment of N1E-115 neuroblastoma cells by acting as a scaffold for cell-associated plasminogen activation. Molecular and Cellular Neuroscience, 28(3), 496-508. https://doi.org/10.1016/j.mcn.2004.11.001