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

Research output: Contribution to journalArticle

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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

Fingerprint

Plasminogen
Neuroblastoma
Fibrinolysin
Amyloid
Carboxypeptidase B
Cell Survival
Plasminogen Activators
Amyloid Plaques
Brain Diseases
Tissue Plasminogen Activator
Lysine
Alzheimer Disease
Cell Death
Peptides
Brain
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

β-Amyloid (Aβ) causes detachment of N1E-115 neuroblastoma cells by acting as a scaffold for cell-associated plasminogen activation. / Kranenburg, Onno; Bouma, Barend; Gent, Yoony Y J; Aarsman, Colinda J.; Kayed, Rakez; Posthuma, George; Schiks, Bettina; Voest, Emile E.; Gebbink, Martijn F B G.

In: Molecular and Cellular Neuroscience, Vol. 28, No. 3, 03.2005, p. 496-508.

Research output: Contribution to journalArticle

Kranenburg, Onno ; Bouma, Barend ; Gent, Yoony Y J ; Aarsman, Colinda J. ; Kayed, Rakez ; Posthuma, George ; Schiks, Bettina ; Voest, Emile E. ; Gebbink, Martijn F B G. / β-Amyloid (Aβ) causes detachment of N1E-115 neuroblastoma cells by acting as a scaffold for cell-associated plasminogen activation. In: Molecular and Cellular Neuroscience. 2005 ; Vol. 28, No. 3. pp. 496-508.
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