Alzheimer amyloid beta-peptides exhibit ionophore-like properties in human erythrocytes.
There is growing evidence that the amyloid beta-peptide (beta 1-40) is involved in the aetiology of Alzheimer's disease also implicating an altered calcium homeostasis of affected cells. Beta 1-40 has been proposed to form calcium channels in synthetic bilayer membranes [1]. We wanted to investigate in the present study whether beta 1-40 (or fragments thereof) could act as ionophores in a biological membrane like the one in human erythrocytes. Incubation of the cells for 2 h and 4 h at 37 degrees C together with 6 mumol L-1 of beta 1-40 or of fragments beta 1-28 and beta 25-35, resulted in a significantly decreased energy charge qualitatively similar to the one obtained by a known calcium ionophore (A 23187, 0.05 mumol L-1). Moreover, beta 1-40 and its two fragments induced a significant alteration of 45Ca permeability in human red blood cells of the same type as the one achieved by the calcium ionophore. The ionophoric action of beta 1-40 and its two fragments may lead to an increase of the intracellular calcium ion concentration, in turn resulting in enhanced Ca(2+)-ATPase activity and a decrease in energy charge. This may be valid also for neuronal plasma membranes and could, therefore, be a possible aetiological mechanism in Alzheimer's disease.
Engström
I
I
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
Ronquist
G
G
Pettersson
L
L
Waldenström
A
A
D000244:Adenosine Diphosphate / Q000097:blood; D000249:Adenosine Monophosphate / Q000097:blood; D000255:Adenosine Triphosphate / Q000097:blood; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D007476:Ionophores; D010446:Peptide Fragments; C084358:amyloid beta-protein (1-28); C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D000001:Calcimycin; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium