Increased Striatal mRNA and Protein Levels of the Immunophilin FKBP-12 in Experimental Parkinson's Disease and Identification of FKBP-12-Binding Proteins
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- 作者：Anna Nilsson ; Karl Skö ; ld ; Benita Sjö ; gren ; Marcus Svensson ; Johan Pierson ; Xiaoqun Zhang ; Richard M. Caprioli ; Jos Buijs ; O ; Bjö ; rn Persson ; O ; Per Svenningsson ; Per E.
- 刊名：Journal of Proteome Research
- 出版年：2007
- 出版时间：October 2007
- 年：2007
- 卷：6
- 期：10
- 页码：3952 - 3961
- 全文大小：295K
- 年卷期：v.6,no.10(October 2007)
- ISSN：1535-3907
文摘
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 havebeen 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 spectrometryto study the transcriptional expression as well as protein levels of FKBP-12 in the unilateral6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. The FKBP-12 protein was also detecteddirectly on brain tissue sections using mass spectrometry profiling. We found increased levels of FKBP-12 mRNA and protein in the dorsal and middle part of the 6-OHDA lesioned striatum. Thus, these studiesclearly demonstrate that FKBP-12 is increased in the brain of a common animal model of Parkinson'sdisease (PD). Additionally, we have identified potential binding partners to FKBP-12 that may beimplicated 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 sensortechnology in combination with mass spectrometry. In conclusion, these data strongly suggests thatFKBP-12 is altered in an experimental model of PD.