Beta-amyloid peptides 1-40betaA and 25-35betaA suppress human amylin-mediated death of RINm5F islet beta-cells with distinct actions on fibril formation.
Amyloid deposition is a common feature of Alzheimer's disease and type 2 diabetes related to beta-amyloid peptides (betaA) and human amylin (hA), respectively. Both betaA and hA form aggregates and fibrils and kill cultured cells. To investigate whether betaA and hA display peptide-specific toxicity on cultured islet beta-cells, we examined the effects of (1-40)betaA and (25-35)betaA peptides on hA-mediated cell death and [(125)I-Tyr(37)]hA precipitation. Synthetic hA aggregated in solution and evoked both conformation- and sequence-dependent cell death. While neither (1-40)betaA nor (25-35)betaA was toxic to islet beta-cells, they suppressed hA-evoked cell death in a concentration-dependent and saturable manner. Only (1-40)betaA, but not (25-35)betaA, showed trophic effects on cultured islet beta-cells and inhibited the precipitation of [(125)I]hA caused by hA. These results suggest that (25-35)betaA does not interfere with hA-mediated fibril formation. Suppression of hA-evoked death of cultured pancreatic islet beta-cells by the betaA peptides is likely to occur through a competing interaction at these cells.
Bai
Ji-Zhong
JZ
Department of Physiology, School of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. j.bai@auckland.ac.nz
D000682:Amyloid / Q000378:metabolism* / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects*; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats
D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D010455:Peptides; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35)