REGULATION OF APOLIPOPROTEIN-E GENE-EXPRESSION AFTER INJURY OF THE RAT SCIATIC-NERVE
REGULATION OF APOLIPOPROTEIN-E GENE-EXPRESSION AFTER INJURY OF THE RAT SCIATIC-NERVE
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DOI：
10.1002/jnr.490250203
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发表时间：
1990-02-01
影响因子：
4.2
通讯作者：
PODUSLO, JF
中科院分区：
文献类型：
--
作者：
LEBLANC, AC;PODUSLO, JF
周围神经损伤后载脂蛋白E（apoE）的表达显著增加。这种增加的表达被认为在随后的轴突再生过程中受到未知机制的负面影响（Muller等人：Science 228：499-501，1985）。本研究探讨再生轴突在调节载脂蛋白E基因表达的作用，在两个实验范式，允许或阻止轴突再生的成年大鼠坐骨神经挤压或永久性横断损伤。这两种模型中的神经经历轴突变性、脱髓鞘和雪旺细胞增殖;然而，随后的轴突再生和髓鞘再形成仅发生在挤压损伤的远段中，而不发生在永久性横断的神经中。两种模型中apo E mRNA的稳态水平在伤后14 d急剧升高，12-14 d达到最高水平，14 ~ 35 d无明显变化。未观察到压伤和永久横断神经之间载脂蛋白E mRNA的稳态水平随损伤后时间的变化有显著差异。在两种模型中，神经内膜段中apo E的稳态蛋白水平最初增加，在损伤后14-21天达到峰值，然后在35 - 60天之间下降。相比之下，在永久性横断后35 - 60天，新翻译和分泌的apo E的速率显著增加了4倍（P < 0.005），而挤压伤后在这些时间没有显著差异。与挤压损伤后观察到的恒定速率相比，横断后载脂蛋白E的翻译和分泌速率增加，以及两种模型中载脂蛋白E mRNA和蛋白的稳态水平相当，表明再生轴突的翻译或翻译后控制，但不是转录和/或转录后控制。此外，永久性横断后载脂蛋白E的生物合成和分泌速率的增加伴随着蛋白质稳态水平的降低，这表明载脂蛋白E要么从神经内膜中去除，要么随后通过独立于神经再生的机制被利用或降解。
The expression of apolipoprotein E (apo E) is dramatically increased following peripheral nerve injury. This increased expression has been postulated to be negatively influenced by unknown mechanisms during subsequent axonal regeneration (Muller et al.: Science 228:499-501, 1985). The present study investigates the role of the regenerating axon in regulating apo E gene expression in two experimental paradigms which permit or prevent axonal regeneration in the adult rat sciatic nerve-the crush or permanent transection injuries. The nerves in these two models undergo axonal degeneration, demyelination, and Schwann cell proliferation; however, subsequent axonal regeneration and remyelination occur only in the distal segment of the crush-injured and not in the permanently transected nerve. The steady-state levels of apo E mRNA in both models increase sharply between 1 and 4 days and reach a maximum level at 12-14 days, which did not change significantly between 14 and 35 days after injury. No significant difference is observed in the steady-state levels of apo E mRNA between the crushed and permanently transected nerves as a function of time after injury. The steady-state protein level of apo E in the endoneurial segments initially increases, peaks at 14-21 days, and then decreases between 35 and 60 days after injury in both models. In contrast, the rate of newly translated and secreted apo E significantly increases by fourfold (P < 0.005) between 35 and 60 days after permanent transection whereas it does not significantly differ at these times after crush injury. The increased rate of translation and secretion of apo E after transection compared to the constant rate observed after crush injury, together with the comparable steady-state levels of apo E mRNA and protein in both models, suggests translational or post-translational control, but not transcriptional and/or posttranscriptional control, by the regenerating axons. Furthermore, the increasing rate of biosynthesis and secretion of apo E after permanent transection concomitant with the decreasing steady-state levels of the protein suggests that apo E is either removed from the endoneurium or subsequently utilized or degraded by mechanisms that are independent from nerve regeneration.