Nitric oxide-proton stimulation of trigeminal ganglion neurons increases mitogen-activated protein kinase and phosphatase expression in neurons and satellite glial cells.

Nitric oxide-proton stimulation of trigeminal ganglion neurons increases mitogen-activated protein kinase and phosphatase expression in neurons and satellite glial cells.
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DOI:
10.1016/j.neuroscience.2008.09.035
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发表时间:
2008-12-02
期刊:
影响因子:
3.3
通讯作者:
Durham PL
Durham PL
中科院分区:
医学3区
文献类型:
--
作者:
Freeman SE;Patil VV;Durham PL

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滑膜液中一氧化氮(NO)和质子水平升高与关节病理有关。然而,这些分子刺激的介导颞下颌关节(TMJ)炎症和疼痛的信号通路尚未被研究。本研究的目的是确定no质子刺激三叉神经细胞对三叉神经节神经元和卫星胶质细胞中丝裂原活化蛋白激酶(MAPKs)和磷酸酶(MKPs)在体内表达的影响。在未受刺激的动物中,低水平的活性MAPKs ERK、JNK和p38定位于神经元和卫星胶质细胞的胞浆中。然而,在双侧TMJ注射pH 5.5培养基稀释的NO供体15分钟和2小时后,在V3神经元和卫星胶质细胞的细胞质和细胞核中检测到活性ERK和p38水平升高,但未检测到JNK水平。刺激24小时后,ERK水平恢复到接近基础水平,p38水平仍显著升高。与MKP-2和MKP-3在神经元或卫星神经胶质细胞中几乎检测不到的水平相反,MKP-1在未刺激动物的神经节卫星神经胶质细胞中很容易观察到染色。然而,神经元和卫星胶质细胞对MKP-1、MKP-2和MKP-3的染色都对no -质子有显著的反应。位于神经节V2和V1区域的神经元和卫星胶质细胞也检测到活性ERK和p38水平升高以及MKP水平升高。我们的数据提供了证据,表明no质子刺激V3神经元导致神经节所有区域活性ERK、p38和MKPs表达的时空变化。我们认为,在三叉神经节中,这些参与外周致敏以及控制炎症和伤害反应的细胞事件可能在颞下颌关节病理中发挥作用。
Elevated nitric oxide (NO) and proton levels in synovial fluid are implicated in joint pathology. However, signaling pathways stimulated by these molecules that mediate inflammation and pain in the temporomandibular joint (TMJ) have not been investigated. The goal of this study was to determine the effect of NO-proton stimulation of trigeminal neurons on the in vivo expression of mitogen-activated protein kinases (MAPKs) and phosphatases (MKPs) in trigeminal ganglion neurons and satellite glial cells. Low levels of the active MAPKs ERK, JNK, and p38 were localized in the cytosol of neurons and satellite glial cells in unstimulated animals. However, increased levels of active ERK and p38, but not JNK, were detected in the cytosol and nucleus of V3 neurons and satellite glial cells 15 min and 2 h following bilateral TMJ injections of a NO donor diluted in pH 5.5 medium. While ERK levels returned to near basal levels 24 h after stimulation, p38 levels remained significantly elevated. In contrast to MKP-2 and MKP-3 levels that were barely detectable in neurons or satellite glial cells, MKP-1 staining was readily observed in satellite glial cells in ganglia from unstimulated animals. However, neuronal and satellite glial cell staining for MKP-1, MKP-2, and MKP-3 were all significantly increased in response to NO-protons. Increased active ERK and p38 levels as well as elevated MKP levels were also detected in neurons and satellite glial cells located in V2 and V1 regions of the ganglion. Our data provide evidence that NO-proton stimulation of V3 neurons results in temporal and spatial changes in expression of active ERK and p38 and MKPs in all regions of the ganglion. We propose that in trigeminal ganglia these cellular events, which are involved in peripheral sensitization as well as control of inflammatory and nociceptive responses, may play a role in TMJ pathology.
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发表时间: 2006-08-02
影响因子: 5.3
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发表时间: 2001-03-01
期刊: NATURE
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作者:
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