CGRP stimulation of iNOS and NO release from trigeminal ganglion glial cells involves mitogen-activated protein kinase pathways.
CGRP stimulation of iNOS and NO release from trigeminal ganglion glial cells involves mitogen-activated protein kinase pathways.
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DOI：
10.1111/j.1471-4159.2009.06154.x
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发表时间：
2009-08
影响因子：
4.7
通讯作者：
Durham PL
中科院分区：
文献类型：
--
作者：
Vause CV;Durham PL
临床和基础科学数据支持降钙素基因相关肽（CGRP）在颞下颌关节紊乱病的病理生理学中的不可或缺的作用。最近，我们发现CGRP可以刺激三叉神经节神经胶质细胞合成和释放一氧化氮（NO）。本研究的目的是确定MAP激酶信号通路在CGRP调节Sprague-Dawley大鼠三叉神经节神经胶质细胞iNOS表达和NO释放中的作用。CGRP处理2小时显著增加MAP激酶报告基因Elk、ATF-2和CHOP的活性。此外，CGRP增加了MAP激酶ERK、JNK和p38活性形式的核染色。在用CGRP受体拮抗剂肽CGRP 8 -37预处理的培养物中未观察到这种刺激事件。同样地，用选择性MAP激酶抑制剂预处理抑制了报告基因活性的增加以及CGRP诱导的MAP激酶介导的iNOS表达和NO释放的增加。此外，MEK 1、MEK 3、MEK 6和MEKK的过表达显著增加了胶质细胞中iNOS的表达和NO的产生。我们的研究结果提供了证据表明，CGRP结合其受体可以刺激诱导型一氧化氮合酶基因的表达，通过激活的MAP激酶途径在三叉神经节胶质细胞。
Clinical and basic science data support an integral role of calcitonin gene-related peptide (CGRP) in the pathophysiology of temporomandibular joint disorders. Recently, we have shown that CGRP can stimulate the synthesis and release of nitric oxide (NO) from trigeminal ganglion glial cells. The goal of this study was to determine the role of MAP kinase signaling pathways in CGRP regulation of iNOS expression and NO release from cultured trigeminal ganglion glial cells from Sprague-Dawley rats. CGRP treatment for 2 hrs significantly increased activity of the MAP kinase reporter genes, Elk, ATF-2, and CHOP. In addition, CGRP increased nuclear staining for the active forms of the MAP kinases ERK, JNK, and p38. This stimulatory event was not observed in cultures pretreated with the CGRP receptor antagonist peptide CGRP8-37. Similarly, pretreatment with selective MAP kinase inhibitors repressed increases in reporter gene activity as well as CGRP-induced increases in iNOS expression and NO release mediated by MAP kinases. In addition, over-expression of MEK1, MEK3, MEK6, and MEKK significantly increased iNOS expression and NO production in glial cells. Results from our study provide evidence that CGRP binding to its receptor can stimulate iNOS gene expression via activation of MAP kinase pathways in trigeminal ganglion glial cells.
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DOI：
10.1016/j.bbapap.2005.08.017
发表时间：
2005-12-30
影响因子：
3.2
作者：
Kaminska, B
通讯作者：
Kaminska, B
影响因子：
9.9
作者：
Ho, T. W.;Mannix, L. K.;Rapoport, A. M.
通讯作者：
Rapoport, A. M.
影响因子：
4.7
作者：
Bhat, NR;Shen, Q;Fan, F
通讯作者：
Fan, F
影响因子：
4.8
作者：
Bhat, NR;Feinstein, DL;Bhat, AN
通讯作者：
Bhat, AN
降钙素基因相关肽促进雪旺细胞增殖。
影响因子：
7.8
作者：
Cheng, L;Khan, M;Mudge, A W
通讯作者：
Mudge, A W