Lead-induced cell death of human neuroblastoma cells involves GSH deprivation.
Lead (Pb2+) is a toxic heavy metal that has adverse effects on the health of humans and other animals. The developing central nervous system is especially sensitive and vulnerable to Pb2+ toxicity. In this study, the effects of low levels of Pb2+ exposure on human SH-SY5Y neuroblastoma cell cultures were assessed. The cells were exposed to Pb2+ (0.01 microM-10 microM) for 48 hrs, and the level of cell proliferation was determined. Pb2+ significantly inhibited the proliferation of neuroblastoma cells in a concentration-dependent manner. A 50% inhibition (IC50) in cellular proliferation was observed with 5 microM Pb2+. A significant decrease in the levels of glutathione (GSH), a critical intracellular antioxidant, was observed at all the lead concentrations. There was also a multifold increase in the activity of caspase-3, a key executioner of apoptosis, and in the levels of prostaglandin E2 (PGE2). Our results suggest that the neurotoxic effects of Pb may be mediated by apoptosis and PGE2 release, which could be potentially detrimental to neuronal survival.
Chetty
Chellu S
CS
Department of Natural Sciences and Mathematics, Savannah State University, Savannah, GA 31404, USA. chettyc@savstate.edu
Vemuri
Mohan C
MC
Campbell
Khamisi
K
Suresh
Challa
C
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D005978:Glutathione / Q000032:analysis / Q000172:deficiency* / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007854:Lead / Q000633:toxicity*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology
D007854:Lead; D006735:Horseradish Peroxidase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D015232:Dinoprostone