Toxic effect of the beta-amyloid precursor protein C-terminus fragment and Na+/Ca2+ gradients.
There is evidence to suggest that certain metabolic fragments of the beta-amyloid precursor protein (betaAPP) containing the whole of the beta-amyloid (Abeta) sequence are toxic to cells. We showed previously that the 105-amino acid C-terminal peptide (CT105) fragment, incorporating Abeta, is particularly toxic to Xenopus oocytes as well as to mammalian neurons. Here, we investigated the contributions of Na+ and Ca2+ gradients to intracellular CT105-induced toxicity in oocytes, monitored by measuring the membrane resting potential. The concentration gradients of Na+ and Ca2+ were manipulated to determine the involvement of the trans-membrane concentration gradients of these ions in the mode of action of CT105. The results suggested that Na+ influx and intracellular events are mainly responsible for the observed CT105-induced toxicity.
Bryan-Sisneros
A A
AA
Imperial College of Science, Technology and Medicine, Department of Biology, London, UK.
Fraser
S P
SP
Suh
Y H
YH
Djamgoz
M B
MB
D016564:Amyloid beta-Protein Precursor / Q000506:poisoning*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D007552:Isotonic Solutions; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000506:poisoning; D000077331:Ringer's Solution; D012964:Sodium / Q000378:metabolism*; D014981:Xenopus
D016564:Amyloid beta-Protein Precursor; D007552:Isotonic Solutions; D010446:Peptide Fragments; D000077331:Ringer's Solution; D012964:Sodium; D008274:Magnesium; D002118:Calcium