NMDA-receptor activation and nitroxidative regulation of the glutamatergic pathway during nociceptive processing.
NMDA-receptor activation and nitroxidative regulation of the glutamatergic pathway during nociceptive processing.
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DOI：
10.1016/j.pain.2010.01.015
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发表时间：
2010-04
期刊：
影响因子：
7.4
通讯作者：
Salvemini D
中科院分区：
文献类型：
--
作者：
Chen Z;Muscoli C;Doyle T;Bryant L;Cuzzocrea S;Mollace V;Mastroianni R;Masini E;Salvemini D
过氧亚硝酸盐(PN)作为伤害性信号的中介体的作用正在显现。我们最近报道，大鼠足底注射角叉菜胶后中枢敏感化的发展与脊髓PN合成有关。我们现在证明，脊髓PN调节中枢敏化的一个重要途径是谷氨酸能途径中涉及的关键蛋白，即谷氨酸转运体GLT-1和谷氨酰胺合成酶(GS)的翻译后酪氨酸硝化。我们还揭示，在这种情况下，N-甲基-D-天冬氨酸(NMDA)受体的脊髓激活提供了PN的来源。足底注射角叉菜胶可引起大鼠热痛觉过敏以及背角组织中GLT-1和GS的硝化。预先给予PN分解催化剂FeTM-4-PYP5+[Fe(III)5，10，15，20-tetrakis(N-methylpyridinium-4-yl)porphyrin]或NMDA受体拮抗剂MK-801可阻断痛觉过敏的发展。角叉菜胶引起的痛敏也与脊髓线粒体超氧化物歧化酶(MnSOD)的硝化和失活有关，已知的MnSOD是中枢敏化过程中PN的关键来源。GLT1和GS的硝化通过增强谷氨酸的神经传递而促进中枢敏化。我们的结果支持了氮氧化应激在痛觉过敏发展中的关键作用，并表明与谷氨酸能神经传递相关的酶和转运体的翻译后硝化是中枢敏化的一种新机制。
The role of peroxynitrite (PN) as a mediator of nociceptive signaling is emerging. We recently reported that the development of central sensitization that follows the intraplantar injection of carrageenan in rats is associated with spinal PN synthesis. We now demonstrate that a significant pathway through which spinal PN modulates central sensitization is post-translational tyrosine nitration of key proteins involved in the glutamatergic pathway, namely glutamate transporter GLT-1 and glutamine synthetase (GS). We also reveal that spinal activation of the N-methyl-D-aspartate (NMDA) receptor provides a source of PN in this setting. Intraplantar injection of carrageenan led to the development of thermal hyperalgesia as well as nitration of GLT-1 and GS in dorsal horn tissues. Pretreatment with the PN decomposition catalyst FeTM-4-PyP5+ [Fe(III)5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin] or the NMDA receptor antagonist MK-801 blocked the development of hyperalgesia. Carrageenan-induced hyperalgesia was also associated with nitration and inactivation of spinal mitochondrial superoxide dismutase (MnSOD) known to provide a critical source of PN during central sensitization. Nitration of GLT1 and GS contributes to central sensitization by enhancing glutamateric neurotransmission. Our results support the critical role of nitroxidative stress in the development of hyperalgesia and suggest that post-translational nitration of enzymes and transporters linked to glutamatergic neurotransmission represent a novel mechanism of central sensitization.
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DOI：
10.1073/pnas.96.14.7731
发表时间：
1999-07-06
影响因子：
11.1
作者：
Mayer, DJ;Mao, JR;Price, DD
通讯作者：
Price, DD
影响因子：
3.9
作者：
MacMillan-Crow, LA;Thompson, JA
通讯作者：
Thompson, JA
DOI：
10.1124/jpet.301.2.478
发表时间：
2002-05-01
影响因子：
3.5
作者：
McInnis, J;Wang, C;Johnson, KM
通讯作者：
Johnson, KM
影响因子：
7.3
作者：
Fraser, CM;Sills, GJ;Brodie, MJ
通讯作者：
Brodie, MJ
影响因子：
2.5
作者：
KITTO, KF;HALEY, JE;WILCOX, GL
通讯作者：
WILCOX, GL