A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.
A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI.
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DOI：
10.1371/journal.pone.0015430
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发表时间：
2010-11-08
期刊：
影响因子：
3.7
通讯作者：
Ishima T
中科院分区：
文献类型：
--
作者：
Hashimoto K;Ishima T
米诺环素是第二代四环素抗生素，具有治疗多种神经退行性疾病和精神疾病的潜在活性。然而，其作用机制仍有待确定。我们发现米诺环素（而非四环素）以浓度依赖性方式显着增强神经生长因子 (NGF) 诱导的 PC12 细胞中的神经突生长。此外，我们发现内质网蛋白肌醇1,4,5-三磷酸（IP3）受体和几种常见信号分子（PLC-γ、PI3K、Akt、p38 MAPK、c-Jun N末端激酶（JNK）、哺乳动物雷帕霉素靶点（mTOR）和Ras/Raf/ERK/MAPK通路）可能参与米诺环素的活性机制。此外，我们发现米诺环素（而非四环素）显着增加真核翻译起始因子 eIF4AI 蛋白，可能参与 NGF 诱导神经突生长的活性机制。这些发现表明 eIF4AI 可能在米诺环素的新机制中发挥作用。因此，能够增加eIF4AI蛋白的药物将成为某些神经退行性疾病和精神疾病的新型治疗药物。
Minocycline, a second-generation tetracycline antibiotic, has potential activity for the treatment of several neurodegenerative and psychiatric disorders. However, its mechanisms of action remain to be determined. We found that minocycline, but not tetracycline, significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells, in a concentration dependent manner. Furthermore, we found that the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP3) receptors and several common signaling molecules (PLC-γ, PI3K, Akt, p38 MAPK, c-Jun N-terminal kinase (JNK), mammalian target of rapamycin (mTOR), and Ras/Raf/ERK/MAPK pathways) might be involved in the active mechanism of minocycline. Moreover, we found that a marked increase of the eukaryotic translation initiation factor eIF4AI protein by minocycline, but not tetracycline, might be involved in the active mechanism for NGF-induced neurite outgrowth. These findings suggest that eIF4AI might play a role in the novel mechanism of minocycline. Therefore, agents that can increase eIF4AI protein would be novel therapeutic drugs for certain neurodegenerative and psychiatric diseases.
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影响因子：
16
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1046/j.1365-2990.2002.t01-1-00410.x
发表时间：
2002-12-01
影响因子：
5
作者：
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