Schipper H M, Kotake Y, Janzen E G
Department of Neurology, McGill University, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
J Neurosci. 1991 Jul;11(7):2170-6. doi: 10.1523/JNEUROSCI.11-07-02170.1991.
In rodents, chronic estrogenization has been shown to induce degeneration of dendrites and myelin figures in the hypothalamic arcuate nucleus adjacent to peroxidase-positive astrocyte processes. Because in this brain region estradiol is metabolized to 2-hydroxyestradiol (catecholestrogen), we hypothesized that the latter may be oxidized by the astrocytic peroxidase activity to cytotoxic ortho-semiquinones as occurs in peripheral tissues. Cysteamine induces nonenzymatic peroxidase activity in cultured astroglia identical to that observed in vivo. Using electron spin resonance, we demonstrate robust peroxidase-catalyzed oxidation of 2-hydroxyestradiol and dopamine by cysteamine-pretreated astrocyte cultures relative to untreated controls. These results implicate the peroxidase-positive astrocytes in the pathogenesis of estradiol-related hypothalamic damage, parkinsonism, and other free-radical-related neurologic disorders.
在啮齿动物中，慢性雌激素化已被证明会诱导下丘脑弓状核中与过氧化物酶阳性星形胶质细胞突起相邻的树突和髓鞘样结构发生退化。由于在这个脑区雌二醇会代谢为2-羟基雌二醇（儿茶酚雌激素），我们推测后者可能会被星形胶质细胞的过氧化物酶活性氧化为细胞毒性邻半醌，就像在周围组织中发生的那样。半胱胺在培养的星形胶质细胞中诱导出与体内观察到的相同的非酶促过氧化物酶活性。利用电子自旋共振，我们证明相对于未处理的对照，半胱胺预处理的星形胶质细胞培养物能使2-羟基雌二醇和多巴胺发生强大的过氧化物酶催化氧化。这些结果表明过氧化物酶阳性星形胶质细胞与雌二醇相关的下丘脑损伤、帕金森病及其他自由基相关神经系统疾病的发病机制有关。
