Inhibitors of nitric oxide synthase attenuate nerve growth factor-mediated increases in choline acetyltransferase expression in PC12 cells
Inhibitors of nitric oxide synthase attenuate nerve growth factor-mediated increases in choline acetyltransferase expression in PC12 cells
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DOI：
10.1046/j.1471-4159.2002.00854.x
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发表时间：
2002-05-01
影响因子：
4.7
通讯作者：
Rylett, RJ
中科院分区：
文献类型：
--
作者：
Kalisch, BE;Bock, NA;Rylett, RJ
神经生长因子可调节一氧化氮合酶（NOS）的表达，一氧化氮（NO）可调节神经生长因子介导的神经营养反应。为了研究NO在NGF激活的胆碱能表型表达中的作用，用非选择性NOS抑制剂L-NAME（N-omega-nitro-L-arginine methylester）或诱导型NOS选择性抑制剂MIU（s-methylisothiourea）处理PC 12细胞，并测定对NGF刺激的ChAT mRNA水平和ChAT比活性的影响。NGF可增加PC 12细胞中诱导型和组成型NOS同工酶mRNA和蛋白的稳态水平，并导致NOS活性和NO产生增加。MIU和L-NAME在较小程度上阻断了神经生长因子（NGF）处理的PC 12细胞中的神经突生长。L-NAME和MIU都减弱了NGF介导的胆碱转移酶（ChAT）特异性活性的增加，并阻止了PC 12细胞正常由NGF处理产生的ChAT mRNA表达的增加。本研究表明，一氧化氮可能参与调制的信号转导途径，通过该途径，NGF导致增加ChAT基因在PC 12细胞中的表达。
NGF can regulate nitric oxide synthase (NOS) expression and nitric oxide (NO) can modulate NGF-mediated neurotrophic responses. To investigate the role of NO in NGF-activated expression of cholinergic phenotype, PC12 cells were treated with either the nonselective NOS inhibitor L-NAME (N-omega-nitro-L-arginine methylester) or the inducible NOS selective inhibitor MIU (s-methylisothiourea), and the effect on NGF-stimulated ChAT mRNA levels and ChAT specific activity was determined. NGF increased steady-state levels of mRNA and protein for both inducible and constitutive isozymes of NOS in PC12 cells, and led to enhanced NOS activity and NO production. MIU and, to a lesser extent, L-NAME blocked neurite outgrowth in nerve growth factor (NGF)-treated PC12 cells. Both L-NAME and MIU attenuated NGF-mediated increases in choline transferase (ChAT)-specific activity and prevented the increase in expression of ChAT mRNA normally produced by NGF treatment of PC12 cells. The present study indicates that NO may be involved in the modulation of signal transduction pathways by which NGF leads to increased ChAT gene expression in PC12 cells.