Enhanced G-protein activation by a mixture of Aβ(25-35), Aβ(1-40/42) and zinc

Zs Molnár, P. Kovács, I. Laczkó, K. Soós, L. Fülöp, B. Penket, Imre Lengyel

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

β-Amyloid peptides (Aβs) bind to several G-protein coupled receptor proteins and stimulate GTPase activity in neurons. In this study we determined the effects of Aβ(1-42), Aβ(1-40), Aβ(25-35) and their mixtures on [35S]GTP binding in rat brain cortical membranes in the absence and presence of zinc. We found that the Aβs alone induced a concentration-dependent activation of G-proteins (IC50 ∼ 10 -6 M), while aggregated Aβ fibrils only affected GTP binding at concentrations above 10-5 M. Mixing Aβ(25-35) with Aβ(1-42) or Aβ(1-40) induced a several-fold increase in GTP-binding. This potentiation followed a bell shaped curve with a maximum at 50: 50 ratios. No potentiating effect could be seen by mixing Aβ(1-40) and Aβ(1-42) or highly aggregated Aβs. Zinc had no effect on Aβ(1-40/42) but strongly potentiated the Aβ(25-35) or the mixed peptides-induced GTP-binding. Changes in secondary structure accompanied the mixed peptides or the peptide/zinc complexes induced potentiation, revealing that structural alterations are behind the increased biological action. These concentration dependent potentiating effects of zinc and the peptide mixtures could be physiologically important at brain regions where peptide fragments and/or zinc are present at elevated concentrations.

Original languageEnglish
Pages (from-to)1215-1223
Number of pages9
JournalJournal of Neurochemistry
Volume89
Issue number5
DOIs
Publication statusPublished - Jun 2004

Fingerprint

GTP-Binding Proteins
Zinc
Guanosine Triphosphate
Chemical activation
Peptides
Brain
Peptide Fragments
GTP Phosphohydrolases
G-Protein-Coupled Receptors
Amyloid
Inhibitory Concentration 50
Neurons
Rats
Membranes
Proteins

Keywords

  • Alzheimer's disease
  • Beta-amyloid peptide
  • Circular dichroism
  • G protein
  • GTP-binding
  • Structure-activity relationship
  • Transmission electron microscopy

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Enhanced G-protein activation by a mixture of Aβ(25-35), Aβ(1-40/42) and zinc. / Molnár, Zs; Kovács, P.; Laczkó, I.; Soós, K.; Fülöp, L.; Penket, B.; Lengyel, Imre.

In: Journal of Neurochemistry, Vol. 89, No. 5, 06.2004, p. 1215-1223.

Research output: Contribution to journalArticle

Molnár, Zs ; Kovács, P. ; Laczkó, I. ; Soós, K. ; Fülöp, L. ; Penket, B. ; Lengyel, Imre. / Enhanced G-protein activation by a mixture of Aβ(25-35), Aβ(1-40/42) and zinc. In: Journal of Neurochemistry. 2004 ; Vol. 89, No. 5. pp. 1215-1223.
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