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.