Peripheral Synthesis of an Atypical Protein Kinase C Mediates the Enhancement of Excitability and the Development of Mechanical Hyperalgesia Produced by Nerve Growth Factor.
Peripheral Synthesis of an Atypical Protein Kinase C Mediates the Enhancement of Excitability and the Development of Mechanical Hyperalgesia Produced by Nerve Growth Factor.
复制标题
DOI：
10.1016/j.neuroscience.2017.12.030
复制
发表时间：
2018-02-10
期刊：
影响因子：
3.3
通讯作者：
Nicol GD
中科院分区：
文献类型：
--
作者：
Kays J;Zhang YH;Khorodova A;Strichartz G;Nicol GD
神经生长因子在炎症反应的启动以及延长疼痛敏感性中起关键作用。以前，我们表明，神经生长因子迅速增强了孤立的大鼠感觉神经元的兴奋性和大鼠后爪的机械敏感性。的兴奋性和敏感性的增加被阻断的肉豆蔻酸化的假底物抑制剂的非典型的蛋白激酶C（mPSI），这表明，一个非典型的蛋白激酶C可能发挥关键的调节作用，在产生这种高度的敏感性。我们的研究结果提出了一个问题，即NGF是否指导翻译控制的变化，如持久的LTP所建议的那样，或者NGF是否通过其他机制导致非典型PKC的激活。目前的研究表明，由NGF产生的增强的动作电位放电被翻译抑制剂阻断，但不被转录抑制剂阻断。同时，体外研究表明，NGF升高PKM β的蛋白水平，这也被翻译抑制剂阻止。在大鼠后爪足底注射神经生长因子产生了快速和持续的机械敏感性的增加，其发病被翻译抑制剂延迟。已建立的NGF诱导的超敏反应可以通过注射雷帕霉素或mPSI暂时逆转。这些结果表明，NGF在爪中产生PKM β蛋白合成的快速增加，其增强神经元敏感性，并且PKM β的持续翻译表达在产生以及维持由NGF产生的提高的敏感性中起关键作用。
Nerve growth factor plays a key role in the initiation as well as the prolonged heightened pain sensitivity of the inflammatory response. Previously, we showed that NGF rapidly augmented both the excitability of isolated rat sensory neurons and the mechanical sensitivity of the rat’s hind paw. The increase in excitability and sensitivity were blocked by the myristolated pseudosubstrate inhibitor of atypical PKCs (mPSI), suggesting that an atypical PKC may play a key regulatory role in generating this heightened sensitivity. Our findings raised the question as to whether NGF directs changes in translational control, as suggested for long-lasting LTP, or whether NGF leads to the activation of an atypical PKC by other mechanisms. The current studies demonstrate that enhanced action potential firing produced by NGF was blocked by inhibitors of translation, but not transcription. In parallel, in vitro studies showed that NGF elevated the protein levels of PKMζ, which was also prevented by inhibitors of translation. Intraplantar injection of NGF in the rat hind paw produced a rapid and maintained increase in mechanical sensitivity whose onset was delayed by translation inhibitors. Established NGF-induced hypersensitivity could be transiently reversed by injection of rapamycin or mPSI. These results suggest that NGF produces a rapid increase in the synthesis of PKMζ protein in the paw that augments neuronal sensitivity and that the ongoing translational expression of PKMζ plays a critical role in generating as well as maintaining the heightened sensitivity produced by NGF.
登录
查看更多内容
影响因子：
2.5
作者：
Hou, WY;Shyu, BC;Sun, WZ
通讯作者：
Sun, WZ
影响因子：
56.9
作者：
Kang, HJ;Schuman, EM
通讯作者：
Schuman, EM
影响因子：
3.3
作者：
Asante, Curtis O.;Wallace, Victoria C.;Dickenson, Anthony H.
通讯作者：
Dickenson, Anthony H.
影响因子：
4.8
作者：
Hernandez, AI;Blace, N;Sacktor, TC
通讯作者：
Sacktor, TC
影响因子：
3.3
作者：
Laferrière A;Pitcher MH;Haldane A;Huang Y;Cornea V;Kumar N;Sacktor TC;Cervero F;Coderre TJ
通讯作者：
Coderre TJ