Amyloid peptide channels: blockade by zinc and inhibition by Congo red (amyloid channel block).
Amyloid peptides are the major constituents of amyloid deposits in various amyloid diseases including Alzheimer's disease, type II diabetes mellitus, prion diseases and others. The hallmark of amyloid is the binding of the dye, Congo red, which creates characteristic staining due to the dye's ability to bind the beta sheet aggregates referred to as amyloid. Previous reports have demonstrated that several cytotoxic, amyloidogenic peptides can form ion channels in planar phospholipid bilayer membranes and have suggested that these channels may represent the pathogenic mechanism of cell and tissue destruction in amyloid disease. Furthermore, zinc and Congo red can ameliorate or prevent the pathogenic effect of certain amyloidpeptides. We report here that zinc at micromolar concentrations caused a reversible blockade of islet amyloid polypeptide (IAPP, amylin) and PrP 106-126 channels whereas calcium and magnesium did not. Congo red completely inhibited channel formation if preincubated with amyloid peptides, but had no effect on IAPP or PrP 106-126 channels once formed. These results suggest a requirement for aggregation for the formation of amyloid peptide channels and are consistent with the "channel hypothesis" of amyloid disease. They also suggest potential avenues for ameliorative therapy of these illnesses.
Hirakura
Y
Y
Department of Psychiatry, Neuropsychiatric Institute, Brain Research Institute and Mental Retardation Research Center, UCLA School of Medicine and West Los Angeles VA Medical Center, CA, USA.
Yiu
W W
WW
Yamamoto
A
A
Kagan
B L
BL
D000682:Amyloid / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D003224:Congo Red / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers; D008274:Magnesium / Q000494:pharmacology; D008954:Models, Biological; D010446:Peptide Fragments / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D017433:Protein Structure, Secondary; D015032:Zinc / Q000494:pharmacology*
D000682:Amyloid; D007473:Ion Channels; D058228:Islet Amyloid Polypeptide; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010743:Phospholipids; D011328:Prions; C082632:prion protein (106-126); D003224:Congo Red; D008274:Magnesium; D015032:Zinc; D002118:Calcium