Publications by authors named "Colinda J Aarsman"

1 Publications

  • Page 1 of 1

Beta-amyloid (Abeta) causes detachment of N1E-115 neuroblastoma cells by acting as a scaffold for cell-associated plasminogen activation.

Mol Cell Neurosci 2005 Mar;28(3):496-508

Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

A major component of neuritic plaques in brain tissue of Alzheimer's disease patients is the beta-amyloid peptide (Abeta). Accumulation of Abeta has been associated with increased neuronal cell death and cognitive decline. We have previously shown that amyloid peptides like Abeta bind tissue-type plasminogen activator (tPA) and stimulate plasmin production. Here we investigated how Abeta regulates plasmin formation by N1E-115 neuroblastoma cells and the effects of Abeta-mediated plasmin formation on cell attachment and cell survival. We find that Abeta 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 Abeta-induced cell detachment independently of direct effects on cell viability. Abeta40 as well as oligomeric and fibrillar forms of Abeta42 stimulated tPA-mediated plasminogen activation and cell detachment. Our results suggest that plasmin-mediated cell detachment could contribute to the pathological effects of Abeta in diseased brain.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
March 2005