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Original Article

Exp Neurobiol 2014; 23(1): 65-76

Published online March 30, 2014

© The Korean Society for Brain and Neural Sciences

Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment

Dong-Ik Shin and Young J. Oh*

Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-2123-2662, FAX: 82-2-312-5657

Received: February 14, 2014; Revised: February 25, 2014; Accepted: February 26, 2014


Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Most cases are sporadic and its etiology is incompletely understood. However, increasing evidence suggests that oxidative stress and mitochondrial dysfunction may be involved in the pathogenesis of Parkinson's disease. The aim of this study was to investigate changes in mitochondrial protein profiles during dopaminergic neuronal cell death using two-dimensional gel electrophoresis in conjunction with mass spectrometry. Several protein spots were found to be significantly altered following treatment of MN9D dopaminergic neuronal cells with 6-hydroxydopamine (6-OHDA). Among several identified candidates, TNF receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone, was released from the mitochondria into the cytosol in MN9D cells as well as primary cultures of dopaminergic neurons following 6-OHDA treatment. This event was drug-specific in that such apoptotic inducers as staurosporine and etoposide did not cause translocation of TRAP1 into the cytosol. To our knowledge, the present study is the first to demonstrate the drug-induced subcellular translocation of TRAP1 during neurodegeneration. Further studies delineating cellular mechanism associated with this phenomenon and its functional consequence may provide better understanding of dopaminergic neurodegeneration that underlies PD pathogenesis.

Keywords: 6-hydroxydopamine, Parkinson’s disease, proteomics, mitochondria, TRAP1
Copyright ©, Experimental Neurobiology 2014.
This is an Open Access article distributed under the terms of the Creative Comm