Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment
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 stre...
| Main Authors: | , |
|---|---|
| Format: | Online |
| Language: | English |
| Published: |
The Korean Society for Brain and Neural Science
2014
|
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984958/ |
| id |
pubmed-3984958 |
|---|---|
| recordtype |
oai_dc |
| spelling |
pubmed-39849582014-04-15 Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment Shin, Dong-Ik Oh, Young J. Original Article 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. The Korean Society for Brain and Neural Science 2014-03 2014-03-27 /pmc/articles/PMC3984958/ /pubmed/24737941 http://dx.doi.org/10.5607/en.2014.23.1.65 Text en Copyright © Experimental Neurobiology 2014. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Shin, Dong-Ik Oh, Young J. |
| spellingShingle |
Shin, Dong-Ik Oh, Young J. Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment |
| author_facet |
Shin, Dong-Ik Oh, Young J. |
| author_sort |
Shin, Dong-Ik |
| title |
Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment |
| title_short |
Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment |
| title_full |
Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment |
| title_fullStr |
Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment |
| title_full_unstemmed |
Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment |
| title_sort |
tumor necrosis factor-associated protein 1 (trap1) is released from the mitochondria following 6-hydroxydopamine treatment |
| description |
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. |
| publisher |
The Korean Society for Brain and Neural Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984958/ |
| _version_ |
1612077492157284352 |