Oleic acid induces GAP-43 expression through a protein kinase C-mediated mechanism that is independent of NGF but synergistic with NT-3 and NT-4/5

Oleic acid induces GAP-43 expression through a protein kinase C-mediated mechanism that is independent of NGF but synergistic with NT-3 and NT-4/5
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油酸通过蛋白激酶 C 介导的机制诱导 GAP-43 表达,该机制不依赖于 NGF,但与 NT-3 和 NT-4/5 具有协同作用

DOI:
10.1016/s0006-8993(03)03253-0
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发表时间:
2003
期刊:
影响因子:
2.9
通讯作者:
J. Medina
J. Medina
中科院分区:
医学3区
文献类型:
--
作者:
Begoña Granda;A. Tabernero;Vega Tello;J. Medina

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我们最近的研究表明,星形胶质细胞中白蛋白的存在触发了油酸的合成和释放,油酸作为神经元的神经营养因子。因此,油酸促进轴突生长、神经元聚集和轴突生长相关蛋白GAP-43的表达。在这项工作中,我们表明,油酸上调GAP-43的表达蛋白激酶C(PKC)依赖的机制。由于GAP-43的表达已被证明是由几个神经营养因子上调,我们研究了油酸和神经生长因子,神经营养因子-3(NT-3)和神经营养因子-4/5(NT-4/5)对GAP-43表达的影响之间的关系。我们的结果表明,NGF不参与油酸的神经营养作用,因为添加NGF并没有改变油酸对GAP-43表达的影响。单独的NT-3和NT-4/5都不能改变GAP-43的表达。然而,NT-3和NT-4/5与油酸协同作用以增加GAP-43表达。与其他神经营养因子相比,缺乏NGF的作用并不意外,因为我们在我们的实验条件下没有发现TrkA表达。油酸对GAP-43表达的影响必须独立于由神经元合成的自分泌因子,因为在低细胞密度下也观察到这种影响。总之,我们的研究结果表明,油酸作为一种神经营养因子,诱导GAP-43的表达通过PKC介导的机制,是不介导的其他神经营养因子,但强烈协同NT-3和NT-4/5。
We have recently shown that the presence of albumin in astrocytes triggers the synthesis and release of oleic acid, which behaves as a neurotrophic factor for neurons. Thus, oleic acid promotes axonal growth, neuronal clustering, and the expression of the axonal growth-associated protein, GAP-43. In this work we show that oleic acid upregulates GAP-43 expression by a protein kinase C (PKC)-dependent mechanism. Since GAP-43 expression has been shown to be upregulated by several neurotrophins, we investigated the relationship between the effect of oleic acid and that of NGF, neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) on GAP-43 expression. Our results indicate that NGF is not involved in the neurotrophic effect of oleic acid because the addition of NGF did not modify the effect of oleic acid on GAP-43 expression. Neither NT-3 nor NT-4/5 alone modified GAP-43 expression. However, NT-3 and NT-4/5 acted synergistically with oleic acid to increase GAP-43 expression. The lack of effect of NGF as compared to other neurotrophins is not unexpected since we have not found TrkA expression under our experimental conditions. The effect of oleic acid on GAP-43 expression must be independent of autocrine factors synthesized by neurons because this effect was also observed at low cellular densities. In conclusion, our results indicate that oleic acid behaves as a neurotrophic factor, inducing GAP-43 expression through a PKC-mediated mechanism that is not mediated by other neurotrophic factors but that is strongly synergized by NT-3 and NT-4/5.
DOI: 10.1016/s0021-9258(19)50567-1
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