Extracellular matrix regulates the amount of the β-amyloid precursor protein and its amyloidogenic fragments

Francisca C. Bronfman, Claudio Soto, Lucia Tapia, Veronica Tapia, Nibaldo C. Inestrosa

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

We have studied the influence of the extracellular matrix (ECM) on the amount of β-amyloid precursor protein (APP) and C-terminal amyloid-bearing fragments in 3T3 fibroblasts. After incubation with ECM components, the cellular APP content of 3T3 cells changed. Besides, different substrata including collagen, fibronectin, laminin, vitronectin, and heparin, determined changes in the amount of a C-terminal 22 kDa-fragment. The regulation of amyloidogenic fragments by the ECM was transient; in fact, when 3T3 cells were plated on tissue culture dishes coated with collagen or vitronectin, maximal levels of the 22 kDa fragment were observed 12 h after plating; in the presence of fibronectin, the maximum level of the amyloidogenic fragment was obtained 36 h after plating. These results indicate that the ECM modulates in a transient way the generation of APP-derived polypeptides containing the amyloid-β-peptide (Aβ). The ECM does not have a generalized effect on 3T3 fibroblasts, because no significant differences in cell attachment, growth rate, whole-cell polypeptide pattern, β1 integrin and α-tubulin levels were observed on cells grown on various matrix proteins. Laminin, collagen, and heparin also influence the level of an amyloidogenic fragment of 35 kDa in Neuro 2A neuronal cells, without a significant change in the neuronal marker acetylcholinesterase. In this case, however, a long-lasting response to ECM molecules was observed. These observations provide evidence that ECM molecules influence APP biogenesis, including the generation of amyloidogenic fragments containing the Aβ peptide. Our studies might prove significant to understand the localized increment of β-amyloid deposition in selected areas of the brain of Alzheimer's patients.

Original languageEnglish
Pages (from-to)360-369
Number of pages10
JournalJournal of Cellular Physiology
Volume166
Issue number2
DOIs
Publication statusPublished - 1 Feb 1996
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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