Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase
Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase
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DOI：
10.1126/science.286.5449.2498
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发表时间：
1999-12-24
期刊：
影响因子：
56.9
通讯作者：
Beckman, JS
中科院分区：
文献类型：
--
作者：
Estévez, AG;Crow, JP;Beckman, JS
在2%的肌萎缩侧索硬化症（ALS）患者中，铜、有色超氧化物歧化酶（SOD）的突变与运动神经元的选择性死亡有关。无论是野生型或ALS突变SOD锌的损失是足以诱导培养的运动神经元凋亡。毒性要求铜与SOD结合，并依赖于内源性一氧化氮的产生。当充满锌，无论是ALS突变型还是野生型铜，锌SOD是有毒的，都保护运动神经元从营养因子撤出。因此，缺锌SOD可能参与偶发性和熟悉ALS的氧化机制，涉及一氧化氮。
Mutations in copper, tint superoxide dismutase (SOD) have been implicated in the selective death of motor neurons in 2 percent of amyotrophic lateral sclerosis (ALS) patients. The loss of zinc from either wild-type or ALS-mutant SODs was sufficient to induce apoptosis in cultured motor neurons. Toxicity required that copper be bound to SOD and depended on endogenous production of nitric oxide. When replete with zinc, neither ALS-mutant nor wild-type copper, zinc SODs were toxic, and both protected motor neurons from trophic factor withdrawal. Thus, zinc-deficient SOD may participate in both sporadic and familiar ALS by an oxidative mechanism involving nitric oxide.