Abstract
Aggregated amyloid peptides (AP), major components of senile plaques, have been considered to play a very important and crucial role in the development and neuro-pathogenesis of Alzheimer's disease (AD). In the present in vitro, study the synergistic effects of Pb(2+), a heavy metal, and AP on the human neuroblastoma SH-SY5Y cells were investigated. The cells treated with Pb(2+) (0.01-10 μM) alone exhibited a significant decrease in viability and IC(50) was 5 μM. A similar decrease in viability was also observed when the cells were exposed to AP, Aβ1-40 (20-120 μM) and Aβ25-35 (2.5-15 μM) for 48 hrs. The IC(50) values were 60 μM and 7.5 μM for Aβ1-40 and Aβ25-35 respectively. To assess the synergistic effects the cells were exposed to IC(50) of both AP and Pb(2+), which resulted in further reduction of the viability. The study was extended to determine the lactate dehydrogenase (LDH) release to assess the cytotoxic effects, 8-isoprostane for extent of oxidative damage, COX 1 and 2 for inflammation related changes, p53 protein for DNA damage and protein kinases A and C for signal transduction. The data suggest that the toxic effects of AP were most potent in the presence of Pb(2+), resulting in an aggravated clinical pathological condition. This could be attributed to the oxidative stress, inflammation neuronal apoptosis and an alteration in the activities of the signaling enzymes.