Kitahara T, Kiryu S, Ohno K, Morita N, Kubo T, Kiyama H
Department of Neuroanatomy, Osaka University Medical School, Japan.
Neurosci Res. 1994 Sep;20(3):275-80. doi: 10.1016/0168-0102(94)90097-3.
Up-regulation of ERK (extracellular signal-regulated kinase or MAP kinase) and MEK (ERK kinase or MAPK kinase) expression after rat facial nerve injury was demonstrated by in situ hybridization histochemistry and immunohistochemistry. These two enzymes play roles in one of the major intracellular signal cascade pathways involving receptor tyrosine kinase common to growth factor receptors, and transcription factors. Significant increases in ERK1 mRNA levels were observed from day 3 after facial nerve transection, with the highest level of expression from 1 to 2 weeks after the operation. This high level of mRNA expression then decreased gradually to the normal level. ERK1-like immunoreactivity showed a similar time course to that of its mRNA expression; however, the decay profile was more prolonged. The up-regulation of MEK, the ERK kinase/MAPK kinase, was also detected by immunohistochemistry. The protein expression profiles were almost equivalent, but the MEK expression was slightly advanced, suggesting that the observed up-regulation of MEK was not due to that of ERK. The receptor tyrosine kinase signal transduction pathway via MEK-ERK located downstream of growth factor receptors seems vital as a regulator of the synthesis of molecules that play important roles in the recovery process following injury or/and regeneration.
通过原位杂交组织化学和免疫组织化学证实,大鼠面神经损伤后细胞外信号调节激酶(ERK,又称丝裂原活化蛋白激酶)和ERK激酶(MEK,又称丝裂原活化蛋白激酶激酶)的表达上调。这两种酶在涉及生长因子受体共有的受体酪氨酸激酶和转录因子的主要细胞内信号级联途径之一中发挥作用。面神经横断后第3天观察到ERK1 mRNA水平显著升高,术后1至2周表达水平最高。然后这种高水平的mRNA表达逐渐下降至正常水平。ERK1样免疫反应性与其mRNA表达呈现相似的时间进程;然而,衰减曲线更为延长。免疫组织化学也检测到ERK激酶/丝裂原活化蛋白激酶激酶MEK的上调。蛋白质表达谱几乎相同,但MEK表达略有提前,这表明观察到的MEK上调并非由ERK上调所致。位于生长因子受体下游的通过MEK-ERK的受体酪氨酸激酶信号转导途径,作为损伤或/和再生后恢复过程中发挥重要作用的分子合成的调节因子似乎至关重要。