Expression and distribution of mTOR, p70S6K, 4E-BP1, and their phosphorylated counterparts in rat dorsal root ganglion and spinal cord dorsal horn.
Expression and distribution of mTOR, p70S6K, 4E-BP1, and their phosphorylated counterparts in rat dorsal root ganglion and spinal cord dorsal horn.
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DOI：
10.1016/j.brainres.2010.04.010
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发表时间：
2010-06-08
期刊：
影响因子：
2.9
通讯作者：
Tao, Yuan-Xiang
中科院分区：
文献类型：
--
作者：
Xu, Ji-Tain;Zhao, Xiuli;Yaster, Myron;Tao, Yuan-Xiang
哺乳动物雷帕霉素靶蛋白（mTOR）控制蛋白质翻译，在持续性疼痛条件下的疼痛超敏反应机制中起重要作用。然而，其在神经系统疼痛相关区域的表达和定位还不完全清楚。在这里，我们研究了mTOR，真核起始因子4 E结合蛋白1/2（4 E-BP 1/2），p70核糖体S6蛋白激酶（p70 S6 K），和他们的磷酸化（活性）在两个主要的疼痛相关区域，背根神经节（DRG）和脊髓背角的表达和分布。逆转录-聚合酶链反应显示mTOR、4 E-BP 1和p70 S6 K mRNA在DRG和背角表达。Western blot分析进一步证实了它们的蛋白产物在这两个区域中的存在，但是它们的磷酸化对应物在背角中的表达非常低，并且在DRG中未检测到。免疫组化显示mTOR和p70 S6 K在DRG神经元中表达。定量分析显示约26.1%（± 3.2%）的DRG神经元表达mTOR，19.1%（± 1.9%）的DRG神经元表达p70 S6 K。这些神经元大多数是小的，横截面积小于600 μm2，并且一些与P物质或isolectin B4共标记。令人惊讶的是，4 E-BP 1仅在DRG卫星神经胶质细胞中观察到。在背角中，mTOR、p70 S6 K和4 E-BP 1在神经元中检测到，但在星形胶质细胞或小胶质细胞中未检测到。它们分布于整个背角，尤其是背角浅部。其磷酸化对应物的免疫染色在DRG和背角中非常低或检测不到。行为学研究表明鞘内注射mTOR抑制剂雷帕霉素对急性病毒传播无影响。结果表明，尽管mTOR、p70 S6 K和4 E-BP 1在DRG和背角中高度表达，但在正常条件下，它们在这两个区域中的激活形式非常低。我们的研究结果支持了mTOR及其下游效应物在急性疼痛中不起关键作用的观点。
Mammalian target of rapamycin (mTOR) controls protein translation and has an important role in the mechanism of pain hypersensitivity under persistent pain conditions. However, its expression and localization in pain-related regions of the nervous system is not completely understood. Here, we examined the expression and distribution of mTOR, eukaryotic initiation factor 4E-binding protein1/2 (4E-BP1/2), p70 ribosomal S6 protein kinase (p70S6K), and their phosphorylated (active) counterparts in two major pain-related regions, the dorsal root ganglion (DRG) and spinal cord dorsal horn. Reverse transcriptase-polymerase chain reaction showed that mTOR, 4E-BP1, and p70S6K mRNA are expressed in the DRG and dorsal horn. Western blot analysis further confirmed the existence of their protein products in these two regions, but expression of their phosphorylated counterparts was very low in dorsal horn and was not detected in the DRG. Immunohistochemistry revealed mTOR and p70S6K in the DRG neurons. Quantitative analysis showed that approximately 26.1% (± 3.2%) of DRG neurons were positive for mTOR and 19.1% (± 1.9%) were positive for p70S6K. Most of these neurons were small—less than 600 μm2 in cross-sectional area—and some co-labeled with substance P or isolectin B4. Surprisingly, 4E-BP1 was observed only in the DRG satellite glial cells. In the dorsal horn, mTOR, p70S6K, and 4E-BP1 were detected in neurons, but not in astrocytes or microglia. They were distributed in the whole dorsal horn, especially in the superficial dorsal horn. Immunostaining for their phosphorylated counterparts was very low or undetectable in DRG and dorsal horn. Behavioral study showed that intrathecal mTOR inhibitor, rapamycin, did not affect acute nocicepetive transmission. The results indicate that although mTOR, p70S6K, and 4E-BP1 are highly expressed in the DRG and dorsal horn, their activate forms are very low in both regions under normal conditions. Our findings support the view that mTOR and its downstream effectors do not play a key role in acute pain.
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影响因子：
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作者：
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发表时间：
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