Ectopic expression of cell cycle markers in models of induced programmed cell death in dopamine neurons of the rat substantia nigra pars compacta
Ectopic expression of cell cycle markers in models of induced programmed cell death in dopamine neurons of the rat substantia nigra pars compacta
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DOI：
10.1006/exnr.2002.8047
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发表时间：
2003-01-01
影响因子：
5.3
通讯作者：
Burke, RE
中科院分区：
文献类型：
--
作者：
El-Khodor, BF;Oo, TF;Burke, RE
越来越多的证据表明，通常参与细胞周期的蛋白质可以调节神经元程序性细胞死亡（PCD）。然而，细胞周期标记物是否在体内正常、有丝分裂后、迁移后的PCD神经元中表达尚不清楚。我们之前已经表明，自然细胞死亡发生在黑质致密部（SNpc）的多巴胺神经元出生后。出生后这些神经元可通过纹状体内注射神经毒素6-羟多巴胺（6-OHDA）或内侧前脑束（MFB）轴切开术诱导PCD。在这些模型诱导死亡时，这些神经元处于长时间的有丝分裂后和迁移后。我们在这些模型中研究了三个细胞周期标记：5-溴-2'-脱氧尿苷（BrdU）结合（S期标记），cdc2蛋白表达（G2期标记）和MPM2 （M期标记）的表达，MPM2是cdc2磷酸化的表位。我们在这里报道，6-OHDA和axo切开术后SNpc中发生PCD的有丝分裂后多巴胺能神经元包含BrdU和过表达cdc2，但不表达MPM2。这是首次在体内证明SNpc的分裂后多巴胺神经元在凋亡过程中表达S期和G2期标志物。这些结果提高了细胞周期调节蛋白可能在帕金森病中多巴胺能神经元的死亡中发挥作用的可能性，PCD一直被假设在其中发挥作用。(C) 2002 Elsevier Science （USA）。
There is increasing evidence that proteins normally involved in the cell cycle can regulate neuronal programmed cell death (PCD). However, it remains unknown whether cell cycle markers are expressed in normal, postmitotic, postmigratory neurons undergoing PCD in vivo. We have previously shown that natural cell death occurs postnatally in dopamine neurons of the substantia nigra pars compacta (SNpc). PCD can be induced postnatally in these neurons either by intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA) or by medial forebrain bundle (MFB) axotomy. At the time of induction of death in these models, these neurons are long postmitotic and postmigratory. We have studied three cell cycle markers in these models: 5-bromo-2'-deoxyuridine (BrdU) incorporation (a marker of S phase), cdc2 protein expression (a marker of G2 phase), and expression of MPM2 (a marker of M phase), an epitope phosphorylated by cdc2. We report here that postmitotic dopaminergic neurons undergoing PCD in the SNpc following 6-OHDA and axotomy lesions incorporate BrdU and overexpress cdc2, but do not express MPM2. This is the first in vivo evidence that postmitotic dopamine neurons of the SNpc undergoing apoptosis express markers for S phase and G2 phase. These results raise the possibility that cell cycle regulatory proteins may play a role in the demise of dopaminergic neurons in Parkinson's disease, in which PCD has been postulated to play a role. (C) 2002 Elsevier Science (USA).