How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons
How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons
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DOI：
10.1074/jbc.m309468200
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发表时间：
2003-12-05
影响因子：
4.8
通讯作者：
Voilley, N
中科院分区：
文献类型：
--
作者：
Mamet, J;Lazdunski, M;Voilley, N
神经生长因子（NGF）是炎症性疼痛的关键因素。它通过上调编码受体、离子通道和神经肽的基因的转录来诱导痛觉过敏。酸敏感离子通道3（ASIC 3）是一种在组织酸中毒过程中由质子门控的去极化钠通道，在感觉神经元中特异性表达。它与心脏缺血性和炎症性疼痛有关。我们以前的研究表明，低内源性神经生长因子是负责ASIC 3基础表达和高神经生长因子在炎症增加ASIC 3表达平行的发展与痛觉过敏相关的神经元过度兴奋。已知NGF通过trkA和p75受体激活许多信号传导途径。我们现在表明：（i）NGF通过组成性激活trkA/磷脂酶C/蛋白激酶C通路控制ASIC 3基础表达，（ii）高度炎症样NGF通过trkA/JNK/p38 MAPK通路和作为转录开关的p75依赖性机制诱导ASIC 3过表达，和（iii）NGF通过ASIC 3编码基因启动子中的AP 1应答元件起作用。这些新的数据表明，潜在的目标，可用于开发新的治疗炎症性疼痛。
Nerve growth factor (NGF) is a key element of inflammatory pain. It induces hyperalgesia by up-regulating the transcription of genes encoding receptors, ion channels, and neuropeptides. Acid-sensing ion channel 3 (ASIC3), a depolarizing sodium channel gated by protons during tissue acidosis, is specifically expressed in sensory neurons. It has been associated to cardiac ischemic and inflammatory pains. We previously showed that low endogenous NGF was responsible for ASIC3 basal expression and high NGF during inflammation increased ASIC3 expression parallely to the development of neuron hyperexcitability associated with hyperalgesia. NGF is known to activate numerous signaling pathways through trkA and p75 receptors. We now show that (i) NGF controls ASIC3 basal expression through constitutive activation of a trkA/phospholipase C/protein kinase C pathway, (ii) high inflammatory-like NGF induces ASIC3 overexpression through a trkA/JNK/ p38MAPK pathway and a p75-dependent mechanism as a transcriptional switch, and (iii) NGF acts through AP1 response elements in ASIC3 encoding gene promoter. These new data indicate potential targets that could be used to develop new treatments against inflammatory pain.