N-Terminal Truncated UCH-L1 Prevents Parkinson's Disease Associated Damage
| العنوان: | N-Terminal Truncated UCH-L1 Prevents Parkinson's Disease Associated Damage |
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| المؤلفون: | Hyun Jung Kim, Youhwa Kim, Sue Hee Huh, Youngmee Kim, Jin Han Nam, Jaeho Jeong, Jae Eun Jeong, Sun Kim, Jawon Seo, Hee-Jung Kim, Jeong Yeob Baek, Kong-Joo Lee, Byung Kwan Jin |
| المصدر: | PLoS ONE PLoS ONE, Vol 9, Iss 6, p e99654 (2014) |
| بيانات النشر: | Public Library of Science, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Proteomics, Male, Parkinson's disease, lcsh:Medicine, Mitochondrion, Biochemistry, chemistry.chemical_compound, Mice, Ubiquitin, Neurobiology of Disease and Regeneration, Enzyme Stability, Medicine and Health Sciences, Monoubiquitination, lcsh:Science, Enzyme Chemistry, Cellular localization, Genetics, Multidisciplinary, Movement Disorders, biology, MPTP, Conjugated Proteins, Brain, Neurodegenerative Diseases, Parkinson Disease, Cell biology, Enzymes, Mitochondria, Neurology, Ubiquitin Thiolesterase, Research Article, Genetically modified mouse, Programmed cell death, Protein Structure, Mice, Transgenic, Protein Chemistry, Enzyme Regulation, Cell Line, Tumor, medicine, Animals, Humans, lcsh:R, Biology and Life Sciences, Proteins, Deuterium Exchange Measurement, Hydrogen Peroxide, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, chemistry, biology.protein, Enzymology, lcsh:Q, Molecular Neuroscience, Protein Processing, Post-Translational, Neuroscience, HeLa Cells |
| الوصف: | Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been proposed as one of the Parkinson's disease (PD) related genes, but the possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant UCH-L1 that we called NT-UCH-L1, in mouse brain tissue as well as in NCI-H157 lung cancer and SH-SY5Y neuroblastoma cell lines. In vivo experiments and hydrogen-deuterium exchange (HDX) with tandem mass spectrometry (MS) studies showed that NT-UCH-L1 is readily aggregated and degraded, and has more flexible structure than UCH-L1. Post-translational modifications including monoubiquitination and disulfide crosslinking regulate the stability and cellular localization of NT-UCH-L1, as confirmed by mutational and proteomic studies. Stable expression of NT-UCH-L1 decreases cellular ROS levels and protects cells from H2O2, rotenone and CCCP-induced cell death. NT-UCH-L1-expressing transgenic mice are less susceptible to degeneration of nigrostriatal dopaminergic neurons seen in the MPTP mouse model of PD, in comparison to control animals. These results suggest that NT-UCH-L1 may have the potential to prevent neural damage in diseases like PD. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::404a845b241978e8562d40fbe2fe0bf1Test http://europepmc.org/articles/PMC4069018Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....404a845b241978e8562d40fbe2fe0bf1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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