L-DOPA reverses the MPTP-induced elevation of the arrestin2 and GRK6 expression and enhanced ERK activation in monkey brain
L-DOPA reverses the MPTP-induced elevation of the arrestin2 and GRK6 expression and enhanced ERK activation in monkey brain
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DOI：
10.1016/j.nbd.2004.10.005
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发表时间：
2005-03-01
影响因子：
6.1
通讯作者：
Gurevich, EV
中科院分区：
文献类型：
--
作者：
Bezard, E;Gross, CE;Gurevich, EV
多巴胺受体（DARs）的失调被认为与帕金森病（PD）病理有关。G蛋白偶联受体（GPCR）通过G蛋白偶联受体激酶（GRKs）激活依赖性磷酸化，然后结合抑制蛋白进行脱敏。通过定量Western blotting，我们检测了四组非人灵长类动物中arrestin2和GRKs的表达差异：(1)正常，(2)帕金森，(3)左旋多巴治疗的帕金森和(4)运动障碍。mptp损伤组大部分脑区Arrestin2、GRK6表达显著升高；GRK2在尾状和内侧苍白球中升高。左旋多巴治疗组与对照组均无显著差异。唯一的运动障碍特异性变化是运动障碍组腹侧纹状体GRK3的升高。MPTP组骤停素和GRK表达的变化伴随着ERK激活的增强和ERK总表达的升高，这也被左旋多巴逆转。这些数据表明，停搏和GRKs参与帕金森病的病理和左旋多巴治疗的效果。(C) 2004爱思唯尔公司版权所有。
Dysregulation of dopamine receptors (DARs) is believed to contribute to Parkinson disease (PD) pathology. G protein-coupled receptors (GPCR) undergo desensitization via activation-dependent phosphorylation by G protein-coupled receptor kinases (GRKs) followed by arrestin binding. Using quantitative Western blotting, we detected profound differences in the expression of arrestin2 and GRKs among four experimental groups of nonhuman primates: (1) normal, (2) parkinsonian, (3) parkinsonian treated with levodopa without or (4) with dyskinesia. Arrestin2 and GRK6 expression was significantly elevated in the MPTP-lesioned group in most brain regions; GRK2 was increased in caudal caudate and internal globus pallidus. Neither levodopa-treated group differed significantly from control. The only dyskinesia-specific change was an elevation of GRK3 in the ventral striatum of the dyskinetic group. Changes in arrestin and GRK expression in the MPTP group were accompanied by enhanced ERK activation and elevated total ERK expression, which were also reversed by L-DOPA. The data suggest the involvement of arrestins and GRKs in Parkinson disease pathology and the effects of levodopa treatment. (C) 2004 Elsevier Inc. All rights reserved.