Alpha and beta estradiol protect neuronal but not native PC12 cells from paraquat-induced oxidative stress
Alpha and beta estradiol protect neuronal but not native PC12 cells from paraquat-induced oxidative stress
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DOI：
10.1007/bf03033216
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发表时间：
2004-01-01
影响因子：
3.7
通讯作者：
Martinoli, MG
中科院分区：
文献类型：
--
作者：
Gélinas, S;Bureau, G;Martinoli, MG
氧化应激目前被认为是几种神经退行性疾病中细胞死亡的介质。值得注意的是，它可能在帕金森病黑质多巴胺神经元的变性中起重要作用。我们研究了一种强氧化剂，除草剂百草枯，使用本地和神经元嗜铬细胞瘤PC 12细胞对细胞窘迫的影响。百草枯给药8小时诱导了一个显着的细胞死亡，在本地和神经元PC 12细胞。由于雌激素的抗氧化特性可以在体外和体内促进神经保护，我们随后研究了雌二醇立体异构体17 α-雌二醇和17 β-雌二醇拯救受到百草枯诱导的氧化应激的PC 12细胞的能力。我们的研究结果表明，两种雌二醇立体异构体在神经元PC 12细胞与百草枯处理的保护作用，而这种效果不能在本地PC 12细胞中观察到。我们还表明，雌激素受体β蛋白的表达调节百草枯管理在本地PC 12细胞，而百草枯不改变神经元PC 12细胞中的雌激素受体β的表达。百草枯还降低了神经元PC 12细胞中的雌激素受体α，从而表明百草枯破坏细胞代谢的新途径。此外，二氢罗丹明-123在百草枯存在下氧化成荧光罗丹明，但在百草枯和17 α-雌二醇或17 β-雌二醇存在下不氧化，维持了两种雌二醇立体异构体可能的直接清除作用。
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 17beta-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 17alpha-estradiol or 17beta-estradiol, sustain a possible direct scavenging role of both estradiol stereoisomers.