NGF promotes copper accumulation required for optimum neurite outgrowth and protein methylation
NGF promotes copper accumulation required for optimum neurite outgrowth and protein methylation
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DOI：
10.1002/neu.20114
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发表时间：
2005-04-01
期刊：
影响因子：
--
通讯作者：
Aletta, JM
中科院分区：
文献类型：
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作者：
Birkaya, B;Aletta, JM
人们对铜在涉及信号转导的生物现象中的作用知之甚少。一个明确的神经元分化细胞模型被用来研究神经生长因子(NGF)信号转导过程中对铜的需求，神经生长因子信号转导导致神经突起生长。实验表明，NGF在治疗3天内增加了细胞内铜的含量。铜络合剂可减少NGF对轴突生长和铜积累的影响。四乙撑五胺(TEPA)是一种铜特异的螯合剂，通过从培养介质中移除和/或添加等摩尔氯化铜，其效果是可逆的。由于先前的工作表明，神经生长因子增加了PC12细胞中的蛋白质甲基化，我们研究了TEPA是否也抑制了S-腺苷同型半胱氨酸水解酶，这是一种参与所有蛋白质甲基化反应的基本铜酶。除了在体外直接抑制SAHH外，我们还发现TEPA降低了PC12细胞和交感神经元中蛋白质精氨酸甲基转移酶1(PRMT1)的特异性酶活性。这些数据构成了第一个生化和细胞证据，以解决铜参与神经元分化的机制。(C)2004年乳清期刊公司。
The role of copper in biological phenomena that involve signal transduction is poorly understood. A well-defined cellular model of neuronal differentiation has been utilized to examine the requirement for copper during nerve growth factor (NGF) signal transduction that results in neurite outgrowth. Experiments demonstrate that NGF increases cellular copper content within 3 days of treatment. Copper chelators reduce the effects of NGF on neurite outgrowth and copper accumulation. The effects of tetraethylene pentamine (TEPA), a copper-specific chelator, are reversible by removal from the culture medium and/or by addition of equimolar copper chloride. Because previous work demonstrated that NGF increases protein methylation in PC12 cells, we examined whether TEPA also inhibits S-adenosylhomocysteine hydrolase (SAHH), an essential copper enzyme involved in all protein methylation reactions. In addition to direct in vitro inhibition of SAHH, we show that TEPA decreases protein arginine methyltransferase 1(PRMT1)specific enzyme activity in PC12 cells and sympathetic neurons. These data comprise the first biochemical and cellular evidence to address the mechanism of copper involvement in neuronal differentiation. (C) 2004 whey Periodicals, Inc.