The effects of beta-estradiol on SHSY5Y neuroblastoma cells during heavy metal induced oxidative stress, neurotoxicity and beta-amyloid secretion.
The role of estrogen as a neurotrophic/neuroprotective agent in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is increasingly being shown. In this study we examine the neuroprotective effects of beta-estradiol on SHSY5Y neuroblastoma cells which have been exposed to the heavy metals cobalt and mercury. The results show that cobalt and mercury are able to induce oxidative stress and cell cytotoxicity and increase the secretion of beta-amyloid 1-40 and 1-42. These deleterious effects are reversed by the pretreatment of cells with beta-estradiol. It is further shown that beta-estradiol exerts its neuroprotective action through mechanisms which reduce oxidative stress and reduce beta-amyloid secretion. Pre-treatment of the cells with alpha-estradiol did not alleviate the toxic effects of the heavy metals. Our results are significant as they contribute to a better understanding of the mode of action of estrogen with relevance to its use in the treatment of neurodegenerative disorders.
Olivieri
G
G
Neurobiology Laboratory, Psychiatric University Hospital, CH-4025 Basel, Switzerland. gianfranco.olivieri@pharma.novartis.com
Novakovic
M
M
Savaskan
E
E
Meier
F
F
Baysang
G
G
Brockhaus
M
M
Müller-Spahn
F
F
D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism*; D003035:Cobalt / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D005978:Glutathione / Q000096:biosynthesis; D006801:Humans; D008628:Mercury / Q000633:toxicity; D019216:Metals, Heavy / Q000633:toxicity*; D009447:Neuroblastoma / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D019216:Metals, Heavy; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D003035:Cobalt; D004958:Estradiol; D008628:Mercury; D005978:Glutathione