The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Parkin protects human dopaminergic neuroblastoma cells against dopamine-induced apoptosis
Abstract
Parkinson's disease (PD) is characterized by the selective degeneration of dopaminergic (DA) neurons in substantia nigra pars compacta (SNpc). A combination of genetic and environmental factors contributes to such a specific loss. Among the five PD-linked genes identified so far, parkin, a protein-ubiquitin E3 ligase, appears to be the most prevalent genetic factor in PD. Although a variety of substrates have been identified for parkin, none of them is selectively expressed in nigral DA neurons. It remains unclear how accumulation of these substrates in the absence of functional parkin may cause the selective death of DA neurons in SNpc. Here, we show that overexpression of parkin protected human DA neuroblastoma cell line (SH-SY5Y) against apoptosis induced by DA or 6-OHDA, but not by H(2)O(2) or rotenone. Parkin significantly attenuated dopamine-induced activation of c-Jun N-terminal kinase (JNK) and caspase-3. It also decreased the level of reactive oxygen species (ROS) and protein carbonyls in the cell. Inhibiting DA uptake through dopamine transporter or treating the cell with antioxidants significantly reduced oxidative stress and dopamine toxicity. Furthermore, PD-linked mutations of parkin significantly abrogated the protective effect of wild-type parkin, as well as its ability to suppress ROS and protein carbonylation. These results suggest that parkin protects against dopamine toxicity by decreasing oxidative stress and ensuing activation of apoptotic programs such as the JNK/caspase pathway. This protective function of parkin, which is greatly attenuated by its PD-linked mutations, may be uniquely important for the survival of DA neurons, as they are constantly threatened by oxyradicals produced during dopamine oxidation.
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“This cell line with overexpressing wild-type and mutant Parkin exhibits decreased levels of ROS and resistance to apoptosis induced by 6-hydroxydopamine (Jiang et al. 2004).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Jiang et al. 2004
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Cites
Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., & Wang, X. (1997) · Cell · doi:10.1016/s0092-8674(00)80434-1 · Cited by 7,289
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227
Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
Langston, J. W., Ballard, P., Tetrud, J. W., & Irwin, I. (1983) · Science · doi:10.1126/science.6823561 · Cited by 4,914
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Betarbet, R. S., Sherer, T., MacKenzie, G. M., Garcia‐Osuna, M., Panov, A. V., & Greenamyre, J. T. (2000) · Nature Neuroscience · doi:10.1038/81834 · Cited by 3,770
Biochemical Pathways of Caspase Activation During Apoptosis
Budihardjo, I. I., Oliver, H., Lutter, M. L., Luo, X., & Wang, X. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.269 · Cited by 2,577
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Shimura, H., Hattori, N., Kubo, S.-I., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., et al. (2000) · Nature Genetics · doi:10.1038/77060 · Cited by 2,024 · cited 2×
“Parkin encodes for a protein-ubiquitin E3 ligase (5), which is responsible for catalyzing ubiquitination of many proteins to facilitate their degradation by the 26S proteasome.”
Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death Pathway
Tournier, C., Hess, P., Yang, D. D., Xu, J., Turner, T. K., Nimnual, A., Bar-Sagi, D., Jones, S. N., Flavell, R. A., & Davis, R. J. (2000) · Science · doi:10.1126/science.288.5467.870 · Cited by 1,728
Differential Requirement for Caspase 9 in Apoptotic Pathways In Vivo
Hakem, R., Hakem, A., Duncan, G. S., Henderson, J. T., Woo, M., Soengas, M. S., Elia, A., de la Pompa, J. L., Kägi, D., Khoo, W., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81477-4 · Cited by 1,296
Shimura, H., Schlossmacher, M. G., Hattori, N., Frosch, M. P., Trockenbacher, A., Schneider, R., Mizuno, Y., Kosik, K. S., & Selkoe, D. J. (2001) · Science · doi:10.1126/science.1060627 · Cited by 1,053
Zhang, Y., Gao, J., Chung, K. K. K., Huang, H., Dawson, V. L., & Dawson, T. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.240347797 · Cited by 982
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638
Pathological roles of MAPK signaling pathways in human diseases
Kim, E. K., & Choi, E.-J. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.12.009 · Cited by 2,472
“nergic neurons from several neurotoxins and oxidative stress [103,104].”
BackgroundThe Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845
“SH-SY5Y cells overexpressing wild-type parkin have decreased ROS levels and are relatively protected against apoptosis induced by dopamine or 6-OHDA [300].”
BackgroundMOLECULAR PATHOPHYSIOLOGY OF PARKINSON'S DISEASE
Moore, D. J., West, A. B., Dawson, V. L., & Dawson, T. M. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135718 · Cited by 1,304
“In cultured cells, parkin overexpression may confer protection against dopamine-mediated toxicity possibly by decreasing oxidative stress through an undetermined mechanism, thus potentially linking parkin to the survival of DA neurons (Jiang et al. 2004).”
BackgroundOxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications
Liu, Z., Zhou, T., Ziegler, A. C., Dimitrion, P., & Zuo, L. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/2525967 · Cited by 810
“For instance, mutated parkin may contribute to the pathogenesis of autosomal recessive PD due to its critical roles in suppressing ROS and preventing the formation of neurotoxic proteins caused by ubiquitination [98, 101].”
Background
Metadata
- Authors
- Jiang, H., Ren, Y., Zhao, J., & Feng, J.
- Affiliations
- University at Buffalo, State University of New York (US)
- Corresponding author
- Jiang, Houbo
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-06-15
- Volume
- 13
- Issue
- 16
- Pages
- 1745-1754
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2158511243
- Cited by
- 239
- References
- 37
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 9 · 2022: 8 · 2021: 12 · 2020: 5 · 2019: 9 · 2018: 6 · 2017: 6 · 2016: 11 · 2015: 13 · 2014: 14 · 2013: 18 · 2012: 11
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS041722, NS41722)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- Parkin, Parkinson's disease, dopaminergic neurons, dopamine toxicity, apoptosis, oxidative stress, reactive oxygen species, protein carbonylation, JNK, caspase-3, dopamine transporter, parkin mutations, SH-SY5Y cells, substantia nigra pars compacta, neuroprotection
- MeSH terms
- Dopamine, Enzyme Activation, Humans, Hydrogen Peroxide, Mutation, Neurons, Parkinson Disease, Rotenone, Tumor Cells, Cultured, Blotting, Western, Gene Expression, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Caspases, In Situ Nick-End Labeling, Ubiquitin-Protein Ligases, JNK Mitogen-Activated Protein Kinases, Caspase 3
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