Insulin inhibits amyloid beta-induced cell death in cultured human brain pericytes.
Amyloid-beta (Abeta) deposition in the cerebral arterial and capillary walls is one of the characteristics of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type. In vitro, Abeta1-40, carrying the "Dutch" mutation (DAbeta1-40), induced reproducible degeneration of cultured human brain pericytes (HBP), by forming fibrils at the cell surface. Thus, this culture system provides an useful model to study the vascular pathology seen in Alzheimer's disease. In this study, we used this model to investigate the effects of insulin on Abeta-induced degeneration of HBP, as it has been mentioned previously that insulin is able to protect neurons against Abeta-induced cell-death. The toxic effect of DAbeta1-40 on HBP was inhibited by insulin in a dose-dependent matter. Insulin interacted with Abeta and inhibited fibril formation of Abeta in a cell-free assay, as well as at the cell surface of HBP. Our data indicate that the formation of a fibril network is essential for Abeta-induced cell death in HBP. Additionally, insulin may be involved in the regulation of Abeta fibrillization in AD.
Rensink
Annemieke A M
AA
Department of Neurology, University Medical Centre Nijmegen, The Netherlands.
Otte-Höller
Irene
I
de Boer
Roelie
R
Bosch
Remko R
RR
ten Donkelaar
Hans J
HJ
de Waal
Robert M W
RM
Verbeek
Marcel M
MM
Kremer
Berry
B
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005455:Fluorescent Antibody Technique / Q000379:methods; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D016253:Microscopy, Immunoelectron / Q000379:methods; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D058225:Plaque, Amyloid / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors
D016229:Amyloid beta-Peptides; D007328:Insulin; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D005973:Glutamine; D005947:Glucose