Prooxidant effects of NGF withdrawal and MEK inhibition in sympathetic neurons
Prooxidant effects of NGF withdrawal and MEK inhibition in sympathetic neurons
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DOI：
10.1089/152308603770310301
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发表时间：
2003-10-01
影响因子：
6.6
通讯作者：
Franklin, JL
中科院分区：
文献类型：
--
作者：
Kirkland, RA;Franklin, JL
神经生长因子（NGF）剥夺交感神经元发生凋亡性死亡时，神经源性活性氧（ROS）增加。据报道，NGF通过促分裂原活化蛋白激酶（MEK）/促分裂原活化蛋白（MAP）激酶途径抑制这些细胞中线粒体增加的ROS产生，因为NGF撤回使该途径失活，并且MEK抑制剂PD 98059在NGF存在下增加ROS。我们在这里表明，在细胞培养中用PD 98059处理大鼠交感神经元大大降低了细胞中还原型谷胱甘肽（GSH）的浓度，GSH是一种主要的细胞抗氧化剂。因此，这是可能的，这种抑制剂诱导细胞的促氧化状态，主要是通过减少GSH浓度，而不是通过引起线粒体ROS的生产增加，在神经生长因子维持交感神经元。这些数据表明，MEK/MAP激酶信号通路调节细胞GSH浓度。
An increase of mitochondrial-derived reactive oxygen species (ROS) occurs in nerve growth factor (NGF)-deprived sympathetic neurons undergoing apoptotic death. It has been reported that NGF suppresses increased ROS production by the mitochondria in these cells through a mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein (MAP) kinase pathway because NGF withdrawal inactivates this pathway and the MEK inhibitor, PD98059, increases ROS in the presence of NGF. We show here that treating rat sympathetic neurons in cell culture with PD98059 greatly decreased cellular concentrations of reduced glutathione (GSH), a major cellular antioxidant. Therefore, it is likely that this inhibitor induces a cellular prooxidant state in NGF-maintained sympathetic neurons primarily by decreasing GSH concentration rather than by causing increased mitochondrial ROS production. These data suggest that the MEK/MAP kinase signaling pathway regulates cellular GSH concentration.