Chronic Exposure to Aluminum Impairs Neuronal Glutamate‐Nitric Oxide‐Cyclic GMP Pathway
Chronic Exposure to Aluminum Impairs Neuronal Glutamate‐Nitric Oxide‐Cyclic GMP Pathway
复制标题
长期接触铝会损害神经元谷氨酸-一氧化氮-环 GMP 通路
作者：
C. Cucarella;C. Montoliu;C. Hermenegildo;R. Sáez;L. Manzo;M. Miñana;V. Felipo
翻译后摘要：人类暴露于铝从环境来源和治疗。然而，铝具有神经毒性，被认为是阿尔茨海默病和其他神经系统疾病的可能病因。铝神经毒性的分子机制尚不清楚。我们测试了铝对培养神经元中谷氨酸-一氧化氮-环GMP通路的影响。神经元短期（4小时）或长期（8-14天）暴露于培养基中的50 µM铝，或大鼠产前暴露，即，妊娠期饮用水中含3.7%的硫酸铝。神经元长期（但不是短期）暴露于铝使谷氨酸诱导的一氧化氮合酶活化减少38%，环GMP形成减少77%。由一氧化氮生成剂S-亚硝基-N-乙酰青霉胺诱导的环GMP形成减少了33%。在产前暴露于铝但在培养过程中未暴露于铝的大鼠神经元中，谷氨酸诱导的环GMP形成被抑制了81%，一氧化氮合酶的激活被降低了85%。S-亚硝基-N-乙酰青霉胺诱导的环GMP的形成不受影响。这些结果表明，长期暴露于铝损害谷氨酸诱导的一氧化氮合酶活化和一氧化氮诱导的鸟苷酸环化酶活化。神经元中谷氨酸-一氧化氮-环GMP通路的受损可能导致铝神经毒性。
Abstract: Humans are exposed to aluminum from environmental sources and therapeutic treatments. However, aluminum is neurotoxic and is considered a possible etiologic factor in Alzheimer's disease and other neurological disorders. The molecular mechanism of aluminum neurotoxicity is not understood. We tested the effects of aluminum on the glutamate‐nitric oxide‐cyclic GMP pathway in cultured neurons. Neurons were exposed to 50 µM aluminum in culture medium for short‐term (4 h) or long‐term (8–14 days) periods, or rats were prenatally exposed, i.e., 3.7% aluminum sulfate in the drinking water, during gestation. Chronic (but not short‐term) exposure of neurons to aluminum decreased glutamate‐induced activation of nitric oxide synthase by 38% and the formation of cyclic GMP by 77%. The formation of cyclic GMP induced by the nitric oxide‐generating agent S‐nitroso‐N‐acetylpenicillamine was reduced by 33%. In neurons from rats prenatally exposed to aluminum but not exposed to it during culture, glutamate‐induced formation of cyclic GMP was inhibited by 81%, and activation of nitric oxide synthase was decreased by 85%. The formation of cyclic GMP induced by S‐nitroso‐N‐acetylpenicillamine was not affected. These results indicate that chronic exposure to aluminum impairs glutamate‐induced activation of nitric oxide synthase and nitric oxide‐induced activation of guanylate cyclase. Impairment of the glutamate‐nitric oxide‐cyclic GMP pathway in neurons may contribute to aluminum neurotoxicity.
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DOI：
10.1016/0006-291x(84)91662-0
发表时间：
1984
影响因子：
3.1
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通讯作者：
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DOI：
10.1002/9780470514306.ch15
发表时间：
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期刊：
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影响因子：
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通讯作者：
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影响因子：
56.9
作者：
PERL, DP;GAJDUSEK, DC;GIBBS, CJ
通讯作者：
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影响因子：
3.4
作者：
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通讯作者：
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