Increased striatal mRNA and protein levells of the immunophilin FKBP-12 in experimental Parkinson's disease and identification of FKBP-12-binding proteins
Increased striatal mRNA and protein levells of the immunophilin FKBP-12 in experimental Parkinson's disease and identification of FKBP-12-binding proteins
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DOI：
10.1021/pr070189e
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Andren, Per E.
中科院分区：
文献类型：
--
作者：
Nilsson, Anna;Skold, Karl;Andren, Per E.
FKBP-12是一种12 kDa的FK506结合蛋白(神经免疫亲和素)，作为免疫抑制药物FK506的受体。包括FKBP-12在内的神经免疫亲和素在大脑中含量丰富，已被证明参与逆转神经元退化和防止细胞死亡。本研究利用原位杂交、Western blotting、双向凝胶电泳法和高效电喷雾串联质谱仪等分析技术，对单侧6-羟基多巴胺(6-OHDA)帕金森病大鼠模型中FKBP-12的转录表达和蛋白水平进行了研究。FKBP-12蛋白也直接在脑组织切片上使用质谱图检测到。我们发现，在6-OHDA损毁的纹状体的背侧和中部，FKBP12的mRNA和蛋白水平增加。因此，这些研究清楚地表明，在帕金森病(PD)的常见动物模型中，FKBP-12在大脑中增加。此外，我们利用表面等离子激元共振传感器技术结合质谱仪，确定了可能与帕金森氏病病理生理学有关的潜在的FKBP-12结合伙伴，如阿尔法烯醇化酶、14-3-3 Zeta/Delta、丙酮酸激酶同工酶和热休克蛋白70。总之，这些数据强烈表明FKBP-12在帕金森病的实验模型中发生了改变。
FKBP-12, a 12 kDa FK506-binding protein (neuroimmunophilin), acts as a receptor for the immunosuppressant drug FK506. Neuroimmunophilins, including FKBP-12, are abundant in the brain and have been shown to be involved in reversing neuronal degeneration and preventing cell death. In this report, we have utilized several analytical techniques, such as in situ hybridization, Western blotting, two-dimensional gel electrophoresis, and liquid chromatography electrospray tandem mass spectrometry to study the transcriptional expression as well as protein levels of FKBP-12 in the unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. The FKBP-12 protein was also detected directly on brain tissue sections using mass spectrometry profiling. We found increased levels of FKBP12 mRNA and protein in the dorsal and middle part of the 6-OHDA lesioned striatum. Thus, these studies clearly demonstrate that FKBP-12 is increased in the brain of a common animal model of Parkinson's disease (PD). Additionally, we have identified potential binding partners to FKBP-12 that may be implicated in the pathophysiology of Parkinson's disease, such as alpha-enolase, 14-3-3 zeta/delta, pyruvate kinase isozymes, and heat shock protein 70, using surface plasmon resonance sensor technology in combination with mass spectrometry. In conclusion, these data strongly suggests that FKBP-12 is altered in an experimental model of PD.