Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons
Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons
复制标题
DOI：
10.1111/j.1460-9568.2005.04011.x
复制
发表时间：
2005-04-01
影响因子：
3.4
通讯作者：
McMahon, SB
中科院分区：
文献类型：
--
作者：
Pezet, S;Spyropoulos, A;McMahon, SB
丝氨酸/苏氨酸激酶Akt/PKB参与多种细胞类型的细胞存活信号传导，包括背根神经节（DRG）。然而，它在成人感觉和伤害系统的生理和病理生理条件下的作用知之甚少。在这项研究中，我们发现在幼稚动物中，几乎所有细胞都表达Akt，但只有一小部分小直径神经元表达高水平的磷酸化Akt （p-Akt Ser 473）。在麻醉大鼠足底注射辣椒素激活体内外周伤害感受器，可诱导中小DRG（主要是trpv1阳性神经元）中p-Akt Ser 473的快速发作和时间依赖性增加。此外，电刺激坐骨神经“A”和“C”纤维诱导小、中型DRG神经元胞质p-Akt Ser 473染色增加。使用河豚毒素阻断坐骨神经的神经元活动可降低p-Akt Ser 473的基础水平。培养的DRG神经元证实了Akt在不同细胞区室的磷酸化是由去极化或受体激活触发的，这表明这种作用部分是由磷脂酰肌醇3-激酶介导的。我们的研究结果表明，p-Akt Ser 473是伤害感受器激活的标志，并提示Akt在成人DRG神经元细胞内信号转导中的新作用。
The serine/threonine kinase Akt/PKB has been implicated in cell survival signalling in many cell types, including the dorsal root ganglion (DRG). However, little is known about its role in physiological and pathophysiological conditions in the adult sensory and nociceptive system. In this study, we show that in naive animals almost all cells express Akt but only a subset of small-diameter neurons expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small- and medium-sized DRG, predominantly TRPV1-positive neurons. In addition, electrical stimulation of 'A and C' fibres in the sciatic nerve induced an increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that phosphorylation of Akt in different cellular compartments is triggered by depolarization or receptor activation, and suggested that this effect is mediated in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is a marker of nociceptor activation and suggest a novel role for Akt in the transduction of intracellular signals in adult DRG neurons.