Alpha and beta estradiol protect neuronal but not native PC12 cells from paraquat-induced oxidative stress.
Oxidative stress is currently considered a mediator of cell death in several neurodegenerative diseases. Notably, it may play an important role in the degeneration of dopamine neurons of the substantia nigra in Parkinson's disease. We examined the effect of a strong oxidant, the herbicide paraquat, on cell distress using native and neuronal pheochromocytoma PC12 cells. Paraquat administration for 8 hours induced a significant cellular death in both native and in neuronal PC12 cells. Since the anti-oxidant properties of estrogens may promote neuroprotection in vitro and in vivo, we then investigated the ability of estradiol stereoisomers, 17alpha-estradiol and 17- beta-estradiol, to rescue PC12 cells submitted to paraquat-induced oxidative stress. Our results show a protective effect of both estradiol stereoisomers in neuronal PC12 cells treated with paraquat, whereas this effect could not be observed in native PC12 cells. We also demonstrate that estrogen receptor beta protein expression is modulated by paraquat administration in native PC12 cells, while paraquat does not change estrogen receptor beta ?expression in neuronal PC12 cells. Paraquat also decreases estrogen receptor alpha in neuronal PC12 cells, thus suggesting new routes for paraquat to collapse cellular metabolism. Besides, the oxidation of dihydrodhodamine-123 into fluorescent rhodamine in the presence of paraquat but not in presence of paraquat and 17 alpha-estradiol or 17 beta-estradiol, sustain a possible direct scavenging role of both estradiol stereoisomers.
Neurosciences Research Group, Department of Biochemistry, Université du Québec á Trois-Riviéres, Trois-Riviéres, G9A 5H7, Québec, Canada.
Sylvie
S
Gélinas
Geneviève
G
Bureau
Barbara
B
Valastro
Guy
G
Massicotte
Francesca
F
Cicchetti
Keith
K
Chiasson
Benoît
B
Gagne
Julie
J
Blanchet
Maria-Grazia
MG
Martinoli
D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D007536:Isomerism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D010269:Paraquat / Q000633:toxicity*; D051381:Rats
D018696:Neuroprotective Agents; D004958:Estradiol; D010269:Paraquat