title: Synergistic effects of amyloid peptides and lead on human neuroblastoma cells.
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.
authors.affiliation: Department of Natural Sciences, Savannah State University, Savannah, GA 31404, USA.
authors.forename: Challa
authors.initials: C
authors.lastname: Suresh
authors.forename: Johnny
authors.initials: J
authors.lastname: Johnson
authors.forename: Roshini
authors.initials: R
authors.lastname: Mohan
authors.forename: Chellu S
authors.initials: CS
authors.lastname: Chetty
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D007854:Lead / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D007854:Lead