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视神经损伤后金鱼和大鼠视网膜神经节细胞中JUN、KROX和CREB转录因子的表达与轴突发芽有关。

Expression of JUN, KROX, and CREB transcription factors in goldfish and rat retinal ganglion cells following optic nerve lesion is related to axonal sprouting.

作者信息

Herdegen T, Bastmeyer M, Bähr M, Stuermer C, Bravo R, Zimmermann M

机构信息

II. Physiologisches Institut, Universität Heidelberg, Germany.

出版信息

J Neurobiol. 1993 Apr;24(4):528-43. doi: 10.1002/neu.480240410.

Abstract

Goldfish and rat optic nerves were cut and crushed, respectively, and the expression of the transcription factor proteins c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB was investigated in retinal ganglion cells (RGCs) by immunocytochemistry. Immunoreactivities (IRs) were followed up to 350 days in the goldfish and up to 22 days in the rat. In RGCs of untreated goldfish and rats, all JUN, FOS, and KROX proteins were absent whereas CREB was constitutively expressed. After optic nerve cut in goldfish, a JUN-like immunoreactivity (JUN-IR) appeared in a small number of RGCs of central retina after 24 h, reached a maximum within 5 days, declined after 30 days, and was on a half-maximal level after 50 days. Between 100 and 200 days, JUN-IR was only visible in a few RGCs and was completely absent after 350 days. Specific antibodies against c-JUN, JUN B, and JUN D gave no distinct immunoreactive signal. Thus, we could not determine which member of the JUN family contributed to the JUN-IR. The expression of CREB declined after 5 days. The number of CREB-labeled RGCs was reduced (not significant) and the intensity of labeling faded out. After 50 days, CREB-IR had returned to basal level. c-FOS, FOS B, and KROX-24 could not be detected in goldfish RGCs following optic nerve cut. After optic nerve crush in the rat, c-JUN, JUN D, and KROX-24 appeared in a substantial number of RGCs after 24 h, had a maximal expression after 5 days, and strongly declined after 8 days. c-JUN and KROX-24 were completely absent after 22 days whereas JUN D was still present in a few rat RGCs. The number of CREB-labeled RGCs decreased after 5 days and had declined by 50% after 22 days. Expression of JUN B, c-FOS, FOS B could not be detected in rat RGCs after optic nerve crush. Our data demonstrate that the decrease of CREB and the increase of JUN and KROX-24 transcription factors precedes and parallels both the alteration of de novo protein synthesis and the axonal sprouting, which are long lasting in goldfish and transient in rat.

摘要

分别切断并挤压金鱼和大鼠的视神经,通过免疫细胞化学方法研究视网膜神经节细胞(RGCs)中转录因子蛋白c-JUN、JUN B、JUN D、c-FOS、FOS B、KROX-24和CREB的表达。在金鱼中对免疫反应性(IRs)进行了长达350天的跟踪,在大鼠中进行了长达22天的跟踪。在未处理的金鱼和大鼠的RGCs中,所有JUN、FOS和KROX蛋白均不存在,而CREB呈组成性表达。金鱼视神经切断后,24小时后中央视网膜的少数RGCs中出现JUN样免疫反应性(JUN-IR),5天内达到最大值,30天后下降,50天后降至半最大水平。在100至200天之间,JUN-IR仅在少数RGCs中可见,350天后完全消失。针对c-JUN、JUN B和JUN D的特异性抗体未给出明显的免疫反应信号。因此,我们无法确定JUN家族的哪个成员导致了JUN-IR。5天后CREB的表达下降。CREB标记的RGCs数量减少(不显著),标记强度逐渐减弱。50天后,CREB-IR恢复到基础水平。视神经切断后,在金鱼RGCs中未检测到c-FOS、FOS B和KROX-24。大鼠视神经挤压后,24小时后大量RGCs中出现c-JUN、JUN D和KROX-24,5天后表达达到最大值,8天后强烈下降。22天后c-JUN和KROX-24完全消失,而JUN D仍存在于少数大鼠RGCs中。5天后CREB标记的RGCs数量减少,22天后减少了50%。视神经挤压后,在大鼠RGCs中未检测到JUN B、c-FOS和FOS B的表达。我们的数据表明,CREB的减少以及JUN和KROX-24转录因子的增加先于并与从头蛋白质合成的改变和轴突萌发平行,这在金鱼中是持久的,在大鼠中是短暂的。

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