Miñana M D, Felipo V, Grisolía S
Instituto de Investigaciones Citológicas de la Caja de Ahorros de Valencia, Centro Asociado del CSIC, Spain.
Adv Exp Med Biol. 1990;272:65-80. doi: 10.1007/978-1-4684-5826-8_4.
We have developed an animal model of hyperammonemia consisting of feeding rats a diet containing ammonium acetate. Using this model we have found that hyperammonemia induces tubulin synthesis in brain. Initially tubulin accumulates rapidly (28% after 2 days on diet) and continues increasing but at a slower rate, reaching a 50% increase after 100 days on the diet. The effect is reversible, rats fed the ammonium diet return to normal levels of tubulin two days after withdrawal of the ammonium diet. In contrast to the effect on brain, hyperammonemia did not increase tubulin content in liver or kidney. Moreover, the effect on brain is selective, with maximum increases of tubulin content in hippocampus, septum and reticular formation while other areas such as locus coeruleus and mammillary nucleus are not affected at all. The results presented show that the induction of tubulin is a consequence of an increased polymerization of microtubules which in turn is due to an altered phosphorylation of microtubule-associated proteins.
我们已经建立了一种高氨血症动物模型，方法是给大鼠喂食含醋酸铵的饮食。利用这个模型，我们发现高氨血症会诱导大脑中微管蛋白的合成。最初，微管蛋白迅速积累（喂食饮食2天后增加28%），并持续增加，但速度较慢，喂食饮食100天后增加50%。这种效应是可逆的，停止喂食铵饮食两天后，喂食铵饮食的大鼠微管蛋白水平恢复正常。与对大脑的影响相反，高氨血症并没有增加肝脏或肾脏中的微管蛋白含量。此外，对大脑的影响具有选择性，海马体、隔区和网状结构中的微管蛋白含量增加最多，而蓝斑和乳头体核等其他区域则完全不受影响。给出的结果表明，微管蛋白的诱导是微管聚合增加的结果，而微管聚合增加又是由于微管相关蛋白磷酸化改变所致。
