Hisanaga K, Sagar S M, Sharp F R
Department of Neurology, University of California, San Francisco.
J Neurochem. 1992 May;58(5):1836-44. doi: 10.1111/j.1471-4159.1992.tb10060.x.
c-fos mRNA and Fos-like protein(s) (FLP) are induced in cultured cortical neurons by glutamate, high K+, phorbol ester, basic fibroblast growth factor, Zn2+, and vasoactive intestinal peptide. Glutamate induction of c-fos mRNA and FLP is blocked by noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, and competitive NMDA antagonists, 4-(3-phosphonopropyl)piperazin-2-carboxylic acid and 2-amino-7-phosphonoheptanoate. These antagonists partially block high K(+)-, phorbol ester-, Zn(2+)-, and VIP-induced c-fos mRNA expression, but have no effect on bFGF-induced c-fos mRNA expression. However, both competitive and noncompetitive NMDA antagonists completely block FLP induction by all of these agents without affecting total protein synthesis. Therefore, these NMDA antagonists block FLP translation, without blocking c-fos transcription. It is hypothesized that NMDA receptor activation is required for translation of c-fos mRNA in cortical neurons after stimulation of multiple intracellular signaling pathways. It is possible that NMDA antagonists prevent cortical plasticity by blocking induction of the Fos protein that would normally be induced by neurotrophic factors, neurotransmitters, and neuromodulators.
在培养的皮质神经元中，谷氨酸、高钾、佛波酯、碱性成纤维细胞生长因子、锌离子和血管活性肠肽可诱导c-fos信使核糖核酸（mRNA）和Fos样蛋白（FLP）的产生。非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂MK-801以及竞争性NMDA拮抗剂4-(3-膦酰基丙基)哌嗪-2-羧酸和2-氨基-7-膦酰基庚酸可阻断谷氨酸对c-fos mRNA和FLP的诱导。这些拮抗剂可部分阻断高钾、佛波酯、锌离子和血管活性肠肽诱导的c-fos mRNA表达，但对碱性成纤维细胞生长因子诱导的c-fos mRNA表达没有影响。然而，竞争性和非竞争性NMDA拮抗剂均可完全阻断所有这些物质诱导的FLP产生，且不影响总蛋白合成。因此，这些NMDA拮抗剂可阻断FLP的翻译，而不阻断c-fos的转录。据推测，在多种细胞内信号通路受到刺激后，皮质神经元中c-fos mRNA的翻译需要NMDA受体激活。NMDA拮抗剂有可能通过阻断通常由神经营养因子、神经递质和神经调质诱导的Fos蛋白的产生来阻止皮质可塑性。
