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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Citations
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
Flagged first, then by citations
Cited by
Sorted by citations
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].”
BackgroundDopamine covalently modifies and functionally inactivates parkin
LaVoie, M. J., Ostaszewski, B. L., Weihofen, A., Schlossmacher, M. G., & Selkoe, D. J. (2005) · Nature Medicine · doi:10.1038/nm1314 · Cited by 722
“2e ), consistent with a previous report in SH-SY5Y cell”
ResultWhat Genetics Tells us About the Causes and Mechanisms of Parkinson's Disease
Corti, O., Lesage, S., & Brice, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00022.2010 · Cited by 652
Whitworth, A. J., Theodore, D. A., Greene, J. C., Beneš, H., Wes, P. D., & Pallanck, L. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501078102 · Cited by 421
The role of parkin in familial and sporadic Parkinson's disease
Dawson, T. M., & Dawson, V. L. (2010) · Movement Disorders · doi:10.1002/mds.22798 · Cited by 411
“Manganeseinduced cell death is reduced by parkin overexpression(66) and parkin protects against dopaminergic toxicity.(67) The exact mechanisms of how parkin overexpression protects against a variety of toxic insults is not known, but it seems to be dependent on its E3 ligase activity.”
BackgroundParkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation
Xiong, H., Wang, D., Chen, L., Choo, Y. S., Ma, H., Tang, C., Xia, K., Jiang, W. B., Ronai, Z. A., Zhuang, X., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37617 · Cited by 406
Giorgi, C., Missiroli, S., Patergnani, S., Duszyński, J., Wieckowski, M. R., & Pinton, P. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6223 · Cited by 343
“In contrast, overexpression of parkin in cultured cells prevents mitochondrial swelling and stress-induced apoptosis (84).”
Mitochondria, calcium and cell death: A deadly triad in neurodegeneration
Celsi, F., Pizzo, P., Brini, M., Leo, S., Fotino, C., Pinton, P., & Rizzuto, R. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.02.021 · Cited by 335
“is unknown [102].”
Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps
Levy, O. A., Malagelada, C., & Greene, L. A. (2009) · APOPTOSIS · doi:10.1007/s10495-008-0309-3 · Cited by 300
“This idea is consistent with cell culture studies showing that parkin overexpression reduces JNK phosphorylation and protects cells against 6OHDA-mediated cell death [190].”
Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila
Cha, G., Kim, S., Park, J., Lee, E., Kim, M., Lee, S. B., Kim, J., Chung, J., & Cho, K. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500346102 · Cited by 266
Seirafi, M., Kozlov, G., & Gehring, K. (2015) · The FEBS Journal · doi:10.1111/febs.13249 · Cited by 256
Jiang, H., Ren, Y., Yuen, E. Y., Zhong, P., Ghaedi, M., Hu, Z., Azabdaftari, G., Nakaso, K., Yan, Z., & Feng, J. (2012) · Nature Communications · doi:10.1038/ncomms1669 · Cited by 254
“Measurement of protein carbonyls The levels of protein carbonyls were measured as described befor”
MethodProgrammed Cell Death in Parkinson's DiseasePreprint
Venderová, K., & Park, D. S. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009365 · Cited by 246
“2009) and protects from apoptosis in dopaminergic neurons (Staropoli et al. 2003; Jiang et al. 2004), in 6-OHDA-treated rat (Vercammen et al.”
BackgroundCalí, T., Ottolini, D., Negro, A., & Brini, M. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.01.004 · Cited by 231
“associated with protection from cellular stress and cell cycle regulation [57–59] and overexpression of parkin in cultured cells not only rescued mitochondrial dysfunction caused by PINK1 loss of function, but exerted a cytoprotective role against different toxic stressor [19–23,26].”
BackgroundNeuronal Apoptosis in Neurodegeneration
Okouchi, M., Ekshyyan, O. Y., Maracine, M., & Aw, T. Y. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1511 · Cited by 222
“Increased expression of wild-type parkin also protected neuroblastoma cells against dopamine-induced apoptosis by attenuating dopamine-induced activation of JNK and caspase 3 (147).”
da Costa, C. A., Sunyach, C., Giaime, E., West, A. B., Corti, O., Brice, A., Safe, S. H., Abou‐Sleiman, P. M., Wood, N. W., Takahashi, H., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1981 · Cited by 211
“Parkin is associated with auto‑ somal recessive juvenile forms of Parkinson’s disease 1 and has been characterized as a ubiquitin ligase 2 that acts as a negative modulator of apoptosis, both in vitro and in vivo 3,4 .”
Wang, C., Ko, H. S., Thomas, B., Tsang, F., Chew, K. C. M., Tay, S.-P., Ho, M. W. L., Lim, T. M., Soong, T. W., Pletniková, O., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi413 · Cited by 209
“(17) demonstrated that overexpression of parkin in SH-SY5Y cells significantly reduced the amount of intracellular oxyradicals, suggesting that the protective effect of parkin is afforded by its ability to suppress oxidative stress.”
BackgroundXiong, N., Long, X., Xiong, J., Jia, M., Chen, C., Huang, J., Ghoorah, D., Kong, X., Lin, Z., & Wang, T. (2012) · Critical Reviews in Toxicology · doi:10.3109/10408444.2012.680431 · Cited by 202
“Unlike cultured primary neurons, various rotenone concentrations ranging from 50 nM to 1000 μM were used in previous studies (Wang et al., 2002; Jiang et al., 2004; Pan et al., 2005; Hsuan et al., 2006; Ruan et al., 2010).”
MethodMitochondria Associated Membranes (MAMs): Architecture and physiopathological role
Barazzuol, L., Giamogante, F., & Calí, T. (2021) · Cell Calcium · doi:10.1016/j.ceca.2020.102343 · Cited by 213
The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease
Zuo, L., & Motherwell, M. S. (2013) · Gene · doi:10.1016/j.gene.2013.07.085 · Cited by 200
The ubiquitin E3 ligase parkin regulates the proapoptotic function of Bax
Johnson, B. N., Berger, A. K., Cortese, G. P., & LaVoie, M. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113248109 · Cited by 195
Selective Vulnerability of Dopaminergic Neurons to Microtubule Depolymerization
Ren, Y., Liu, W., Jiang, H., Jiang, Q., & Feng, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503483200 · Cited by 188
Self-citationParkin Mediates Neuroprotection through Activation of IκB Kinase/Nuclear Factor-κB Signaling
Henn, I. H., Bouman, L., Schlehe, J. S., Schlierf, A., Schramm, J. E., Wegener, E., Nakaso, K., Culmsee, C., Berninger, B., Krappmann, D., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5537-06.2007 · Cited by 173
“…cells against cell death induced by kainate, proteasomal inhibition, -synuclein, ceramide, manganese, dopamine, and unfolded protein stress (Imai et al., 2000; Petrucelli et al., 2002; Darios et al., 2003; Staropoli et al., 2003; Higashi et al., 2004; Jiang et al., 2004; Muqit et al., 2004).”
BackgroundMitophagy and Oxidative Stress: The Role of Aging
Gaetano, A. D., Gibellini, L., Zanini, G., Nasi, M., Cossarizza, A., & Pinti, M. (2021) · Antioxidants · doi:10.3390/antiox10050794 · Cited by 196
Targeting autophagy, oxidative stress, and ER stress for neurodegenerative disease treatment
Esmaeili, Y., Yarjanli, Z., Paknia, F., Bidram, E., Łoś, M., Eshraghi, M., Klionsky, D. J., Ghavami, S., & Zarrabi, A. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.001 · Cited by 184
Parkin protects mitochondrial genome integrity and supports mitochondrial DNA repair
Rothfuss, O. C., Fischer, H., Hasegawa, T., Maisel, M., Leitner, P., Miesel, F., Sharma, M., Bornemann, A., Berg, D., Gasser, T., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp327 · Cited by 182
“Consistent with this idea, a decrease of cellular ROS in neuroblastoma cells over-expressing parkin has been reported (31).”
BackgroundAntioxidant gene therapy against neuronal cell death
Navarro-Yepes, J., Zavala-Flores, L. M., Anandhan, A., Wang, F., Skotak, M., Chandra, N., Li, M., Pappa, A., Martínez‐Fong, D., Razo, L. M. D., et al. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.12.007 · Cited by 182
“On the other hand, Parkin protects cells against dopamine toxicity (Jiang et al., 2004).”
Parkin Mono-ubiquitinates Bcl-2 and Regulates Autophagy
Chen, D., Gao, F., Li, B., Wang, H., Xu, Y., Zhu, C., & Wang, G. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.101469 · Cited by 170
Parkin and PINK1 functions in oxidative stress and neurodegeneration
Barodia, S. K., Creed, R. B., & Goldberg, M. S. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.12.004 · Cited by 172
“…such as mitochondrial stress, endoplasmic reticulum stress, excitotoxicity, and proteotoxic stress (Imai et al. 2000; Petrucelli et al. 2002; Darios et al. 2003; Staropoli et al. 2003; Higashi et al. 2004; Jiang et al. 2004; Muqit et al. 2004; Yang et al. 2005; Rosen et al. 2006; Fett et al. 2010).”
BackgroundWeihofen, A., Ostaszewski, B. L., Minami, Y., & Selkoe, D. J. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm334 · Cited by 169
“Of special interest is the finding that overexpression of Parkin, which is known to be protective against several PD-associated insults, including dopamine and a-synuclein mediated neurotoxicity ( 32 ,33), strongly increased the 66/ 55 kDa ratio, whereas DJ-1 had no effect.”
BackgroundAnandhan, A., Jacome, M. S., Lei, S., Hernández-Franco, P., Pappa, A., Panayiotidis, M. I., Powers, R., & Franco, R. (2017) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.03.009 · Cited by 165
Parkin and mitochondrial quality control: toward assembling the puzzle
Winklhofer, K. F. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.01.001 · Cited by 153
Role of the ubiquitin proteasome system in Parkinson's disease
Lim, K., & Tan, J. M. (2007) · BMC Biochemistry · doi:10.1186/1471-2091-8-s1-s13 · Cited by 161
“This is exemplified by its broad neuroprotective capacity, which includes conferring protection against manganese-induced cell death [52], α-synuclein toxicity [53], Pael-R [54] and p38/JTv-1 accumulation [50], kainate-induced excitotoxicity [49], DA-mediated toxicity [ 55 ], and importantly, proteasome dysfunction [4…”
BackgroundC. elegans as a model organism to investigate molecular pathways involved with Parkinson's disease
Harrington, A. J., Hamamichi, S., Caldwell, G. A., & Caldwell, K. A. (2010) · Developmental Dynamics · doi:10.1002/dvdy.22231 · Cited by 150
“Accordingly, in mammals, parkin has been shown to rescue DA neurons against DA or 6-hydroxydopamine (6-OHDA)-induced apoptosis (Jiang et al., 2004; Hasegawa et al., 2008).”
BackgroundRORA, a large common fragile site gene, is involved in cellular stress response
Zhu, Y., McAvoy, S., Kuhn, R. M., & Smith, D. I. (2006) · Oncogene · doi:10.1038/sj.onc.1209314 · Cited by 145
“The re-introduction of WWOX and Parkin into cell lines that do not express them can sometimes inhibit the growth of these cells as well as result in greater sensitivity to apoptotic induction (Bednarek et al., 2001; Jiang et al., 2004; Wang et al., 2004).”
BackgroundNakajima, H., Amano, W., Kubo, T., Fukuhara, A., Ihara, H., Azuma, Y., Tajima, H., Inui, T., Sawa, A., & Takeuchi, T. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.027698 · Cited by 145
Malkus, K. A., Tsika, E., & Ischiropoulos, H. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-24 · Cited by 144
“Parkin overexpression in cultured cells helped prevent mitochondrial swelling, cytochrome c release, caspase 3 activation, increased reactive species levels, and cell death [143,144].”
BackgroundStructure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection
Trempe, J., & Fon, E. A. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00038 · Cited by 136
Laar, V. S. V., & Berman, S. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.05.015 · Cited by 137
Pilsl, A., & Winklhofer, K. F. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0902-3 · Cited by 131
Angeles, D. C., Gan, B.-H., Onstead, L., Zhao, Y., Lim, K., Dächsel, J. C., Melrose, H. L., Farrer, M. J., Wszołek, Z. K., Dickson, D. W., et al. (2011) · Human Mutation · doi:10.1002/humu.21582 · Cited by 133
“…activity, had lost its ability to protect against dopamine-induced oxidative stress, while mutation in the catalytic region of PTEN induced putative kinase 1 (PINK1) resulted in impaired kinase activity on Hsp75 and protection against oxidative stress [Jiang et al., 2004; Pridgeon et al., 2007].”
BackgroundATF4 protects against neuronal death in cellular PD models by maintaining levels of parkin
Sun, X., Liu, J., Crary, J. F., Malagelada, C., Sulzer, D., Greene, L., & Levy, O. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2292-12.2013 · Cited by 123
“Lossof-function mutations in parkin are a relatively common cause of autosomal recessive, early-onset PD. Parkin enhances neuronal survival in numerous model systems (Jiang et al., 2004).”
BackgroundThe role of mitochondria-associated membranes in cellular homeostasis and diseases
Perrone, M., Caroccia, N., Genovese, I., Missiroli, S., Modesti, L., Pedriali, G., Vezzani, B., Vitto, V. A. M., Antenori, M., Lebiedzińska, M., et al. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2019.11.002 · Cited by 132
Parkin Increases Dopamine Uptake by Enhancing the Cell Surface Expression of Dopamine Transporter
Jiang, H., Jiang, Q., & Feng, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409282200 · Cited by 122
Self-citationParkin Phosphorylation and Modulation of Its E3 Ubiquitin Ligase Activity
Yamamoto, A., Friedlein, A., Imai, Y., Takahashi, R., Kahle, P. J., & Haass, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407724200 · Cited by 121
Parkin Protects against Neurotoxicity in the 6-Hydroxydopamine Rat Model for Parkinson's Disease
Vercammen, L., der Perren, A. V., Vaudano, E., Gijsbers, R., Debyser, Z., den Haute, C. V., & Baekelandt, V. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.06.009 · Cited by 118
“In contrast, a more recent report demonstrated a protective effect of parkin overexpression in SH-SY5Y cells against dopamine- and 6-OHDA-induced apoptosis [32].”
BackgroundParkin: a multifaceted ubiquitin ligase
Moore, D. J. (2006) · Biochemical Society Transactions · doi:10.1042/bst0340749 · Cited by 123
Parkin inhibits BAK and BAX apoptotic function by distinct mechanisms during mitophagy
Bernardini, J. P., Brouwer, J. M., Tan, I. K. L., Sandow, J. J., Huang, S., Stafford, C. A., Bankovacki, A., Riffkin, C. D., Wardak, A. Z., Czabotar, P. E., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201899916 · Cited by 126
“Parkin-mediated mitophagy is considered a pro-survival mechanism in response to mitochondrial stress, and Parkin has been reported to prevent apoptosis in a variety of settings (Darios et al , 2003; Staropoli et al , 2003; Jiang et al , 2004; Wang et al , 2007; Berger et al , 2009).”
A critical evaluation of the ubiquitin–proteasome system in Parkinson's disease
Cook, C. N., & Petrucelli, L. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.01.012 · Cited by 119
“In particular taking into consideration that parkin has been shown to exert a significant neuroprotective effect against various toxic insults, including manganese-induced cell death, α-synuclein toxicity, proteasomal dysfunction, Pael-R and P38/JTv-1 accumulation, kainateinduced excitotoxicity, mitochondrial-dependen…”
BackgroundMitochondria Dysfunction and Neurodegenerative Disorders: Cause or Consequence
Morais, V. A., & Strooper, B. D. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100345 · Cited by 111
“chondrial gene transcription and biogenesis in proliferating cells [90,91].”
BackgroundParkin Gene Therapy for α-Synucleinopathy: A Rat Model of Parkinson's Disease
Yamada, M., Mizuno, Y., & Mochizuki, H. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.262 · Cited by 111
“…kainite excitotoxicity, manganese, dopamine, and overexpression of (cid:1) -synuclein (Imai et al ., 2000; Petrucelli et al ., 2002; Darios et al ., 2003; Kim et al ., 2003; Oluwatosin-Chigbu et al ., 2003; Staropoli et al ., 2003; Yang et al ., 2003; Higashi et al ., 2004; Jiang et al ., 2004).”
Parkinsonism genes: culprits and clues
Abeliovich, A., & Beal, M. F. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04102.x · Cited by 110
“…disease genes with common survival signaling components, including the pro- and antiapoptotic Bcl-2 family members (Clark et al. 2006; Park et al. 2006), c-Jun terminal kinase (Jnk) pathway activation (Jiang et al. 2004; Cha et al. 2005), and PTEN signaling pathway components (Kim et al. 2005b).”
BackgroundDagda, R. K., & Chu, C. T. (2009) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-009-9255-1 · Cited by 104
“Parkin’s neuroprotective effects extend beyond its ability to mediate the ubiquitin mediated sequestration and degradation of protein aggregates (Olzmann and Chin 2008), as it promotes autophagy of damaged mitochondria (Narendra et al. 2008; Dagda et al. 2009b), also functioning to increase mitochondrial biogenesis (K…”
BackgroundHatano, T., Kubo, S., Sato, S., & Hattori, N. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06403.x · Cited by 100
“In addition, several groups reported that parkin protects against DA-induced apoptosis in cultured cells (Jiang et al. 2004; Hasegawa et al. 2008b).”
BackgroundPotential autophagy enhancers attenuate rotenone-induced toxicity in SH-SY5Y
Xiong, N., Jia, M., Chen, C., Xiong, J., Zhang, Z., Huang, J., Hou, L., Yang, H., Cao, X., Liang, Z., et al. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.10.031 · Cited by 99
Parkin reverses intracellular β‐amyloid accumulation and its negative effects on proteasome function
Rosen, K. M., Moussa, C., Lee, H., Kumar, P., Kitada, T., Qin, G., Fu, Q., & Querfurth, H. W. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22178 · Cited by 97
“First, Parkin may indirectly reduce sensitivity to amyloid-induced ROS and buildup of peroxidized products while acting at the level of the mitochondrion (Darios et al., 2003; Palacino et al., 2004; Jiang et al., 2004; Kuroda et al., 2006).”
BackgroundSynaptic vesicle trafficking and Parkinson's disease
Esposito, G., Clara, F. A., & Verstreken, P. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20916 · Cited by 95
“, 2010), or parkin loss of function (Jiang et al., 2004), show DA dependent degeneration of DA neurons, further indicating that high cytoplasmatic DA may confer susceptibility to degeneration, but additional work is required.”
BackgroundCheng, M., Liu, L., Lao, Y., Liao, W., Liao, M., Luo, X., Wu, J., Xie, W., Zhang, Y., & Xu, N. (2016) · Oncotarget · doi:10.18632/oncotarget.9786 · Cited by 92
“Increasing evidence has indicated that Parkin shows protective function against apoptosis [48-50].”
BackgroundRen, Y., Jiang, H., Yang, F., Nakaso, K., & Feng, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806245200 · Cited by 87
Self-citationAngeline, M. S., Chaterjee, P., Anand, K., Ambasta, R. K., & Kumar, P. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.06.021 · Cited by 86
“Recent studies have reported that the over expression of parkin in cultured cells enhanced human dopaminergic neuron survival, probably by reducing oxidative stress (Jiang et al., 2004).”
BackgroundBogaerts, V., Theuns, J., & Broeckhoven, C. V. (2007) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2007.00342.x · Cited by 91
“In human DAergic neuroblastoma cells (SH-SY5Y) parkin overexpression Genes, Brain and Behavior (2008) 7: 129–151 135 not only protected against apoptosis, but also decreased cellular ROS levels (Jiang et al. 2004).”
BackgroundParkin functionally interacts with PGC-1α to preserve mitochondria and protect dopaminergic neurons
Zheng, L., Bernard‐Marissal, N., Moullan, N., D'Amico, D. F., Auwerx, J. H., Moore, D. J., Knott, G. W., Aebischer, P., & Schneider, B. L. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw418 · Cited by 86
Sunico, C. R., Nakamura, T., Rockenstein, E. M., Mante, M., Adame, A., Chan, S. F., Newmeyer, T. F., Masliah, E., Nakanishi, N., & Lipton, S. A. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-29 · Cited by 86
“Parkin encodes an E3 ubiquitin ligase [9,10], and disruption in parkin-mediated protein ubiquitination may contribute in part to neuronal cell death [11-16], although other neuroprotective actions of parkin have also been reported [17,18].”
BackgroundParkin Suppresses the Expression of Monoamine Oxidases
Jiang, H., Jiang, Q., Liu, W., & Feng, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510926200 · Cited by 80
“dopaminergic neuroblastoma cell line SH-SY5Y reduces dopamine-induced apoptosis by decreasing ROS production (23).”
InfluentialSelf-citationThymoquinone exerts neuroprotective effect in animal model of Parkinson’s disease
Ebrahimi, S. S., Oryan, S., Izadpanah, E., & Hassanzadeh, K. (2017) · Toxicology Letters · doi:10.1016/j.toxlet.2017.05.018 · Cited by 84
Oxidative stress and Parkinson's disease
Jenner, P. G. (2007) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)83024-7 · Cited by 79
Rahimmi, A., Khosrobakhsh, F., Izadpanah, E., Moloudi, M. R., & Hassanzadeh, K. (2015) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2015.02.007 · Cited by 80
Hasegawa, T., Treis, A., Patenge, N., Fiesel, F. C., Springer, W., & Kahle, P. J. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05277.x · Cited by 78
“However, we find that parkin does protect against tyrosinase-induced oxidative DA toxicity in human neuroblastoma SH-SY5Y cells, consistent with recent reports that parkin can attenuate DA neurotoxicity in this human CNS neuroblastoma cell line (Higashi et al. 2004; Jiang et al. 2004), which may more closely reflect t…”
BackgroundResultInfluentialShenoy, K., Wu, Y., & Pervaiz, S. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-1996 · Cited by 77
Roth, J. A., Singleton, S. T., Feng, J., Garrick, M. D., & Paradkar, P. N. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06607.x · Cited by 74
“Human SH-SY5Y neuroblastoma cells stably transfected with vector, wild-type (Park-WT) and mutant (Park-T240R) forms of human parkin used in these studies were previously generated and characterized by Jiang et al. (2004).”
MethodSelf-citationMutations in PRKN and SNCA Genes Important for the Progress of Parkinson’s Disease
Oczkowska, A., Kozubski, W. P., Lianeri, M., & Dorszewska, J. (2014) · Current Genomics · doi:10.2174/1389202914666131210205839 · Cited by 72
“It has been found that Parkin may downregulate the zinc finger-containing protein called PARIS, which is a major transcriptional repressor of PGC-1 expression [96].”
BackgroundEchinacoside Protects Against MPP+-Induced Neuronal Apoptosis via ROS/ATF3/CHOP Pathway Regulation
Zhao, Q. C., Yang, X., Cai, D., Ye, L., Hou, Y., Zhang, L., Cheng, J., Shen, Y., Wang, K., & Bai, Y. (2016) · Neuroscience Bulletin · doi:10.1007/s12264-016-0047-4 · Cited by 70
SUN, F., KANTHASAMY, A. G., ANANTHARAM, V., & KANTHASAMY, A. G. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.04.001 · Cited by 69
chung, E., Choi, Y., Park, J., Nah, W., Park, J.-H., Jung, Y., Lee, J., Lee, H., Park, S., Hwang, S., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba1193 · Cited by 69
Thomas, B., von Coelln, R., Mandir, A. S., Trinkaus, D. B., Farah, M. H., Lim, K. L., Calingasan, N. Y., Beal, M. F., Dawson, V. L., & Dawson, T. M. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.12.021 · Cited by 67
Parkin-deficient mice are not more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity
Perez, F. A., Curtis, W., & Palmiter, R. D. (2005) · BMC Neuroscience · doi:10.1186/1471-2202-6-71 · Cited by 68
“With regard to the role of Parkin in 6-OHDA toxicity, it has been observed that overexpression of Parkin protects against 6-OHDA toxicity in some cell culture models [31] but not in others [63].”
BackgroundParkin degrades estrogen-related receptors to limit the expression of monoamine oxidases
Ren, Y., Jiang, H., Ma, D., Nakaso, K., & Feng, J. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq550 · Cited by 67
“SH-SY5Y cells stably expressing parkin or its K161N or T240R mutant were generated previously (7).”
BackgroundInfluentialSelf-citationEkholm‐Reed, S., Goldberg, M. S., Schlossmacher, M. G., & Reed, S. I. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00535-13 · Cited by 68
“One of the proposed roles of parkin is to protect neurons from oxidative stress (63, 64).”
BackgroundMitochondrial kinases in Parkinson’s disease: Converging insights from neurotoxin and genetic models
Dagda, R. K., Zhu, J., & Chu, C. T. (2009) · Mitochondrion · doi:10.1016/j.mito.2009.06.001 · Cited by 64
Liang, Q., Smith, A. D., Pan, S., Tyurin, V. A., Kagan, V. E., Hastings, T. G., & Schor, N. F. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.04.011 · Cited by 65
α-Synuclein Aggregates Interfere with Parkin Solubility and Distribution
Kawahara, K., Hashimoto, M., Bar‐On, P., Ho, G. J., Crews, L. A., Mizuno, H., Rockenstein, E. M., Imam, S. Z., & Masliah, E. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710418200 · Cited by 64
Tokarew, J. M., Kodsi, D. N. E., Lengacher, N. A., Fehr, T. K., Nguyen, A., Shutinoski, B., O’Nuallain, B., Jin, M., Khan, J. M., Ng, A. C., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02285-4 · Cited by 64
Wilhelmus, M. M. M., Nijland, P. G., Drukarch, B., de Vries, H. E., & van Horssen, J. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.05.040 · Cited by 62
“ide- and rotenone-induced apoptosis [44].”
Loss of Microglial Parkin Inhibits Necroptosis and Contributes to Neuroinflammation
Dionísio, P. A., Oliveira, S. R., Amaral, J. D., & Rodrigues, C. M. P. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1264-9 · Cited by 65
Trib3 Is Elevated in Parkinson's Disease and Mediates Death in Parkinson's Disease Models
Aimé, P., Sun, X., Zareen, N., Rao, A., Berman, Z., Volpicelli‐Daley, L. A., Bernd, P., Crary, J. F., Levy, O. A., & Greene, L. A. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0614-15.2015 · Cited by 59
“Parkin overexpression protects from Trib3 overexpression and Parkin knockdown reverses the protective effects of Trib3 knockdown in a cellular toxin model Converging evidence indicates a protective role for Parkin overexpression in multiple in vitro (Jiang et al., 2004; Sun et al., 2013) and in vivo (Haque et al.”
BackgroundProfiling of Parkin-Binding Partners Using Tandem Affinity Purification
Zanon, A., Raković, A., Blankenburg, H., Doncheva, N. T., Schwienbacher, C., Serafin, A., Alexa, A., Weichenberger, C. X., Albrecht, M., Klein, C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078648 · Cited by 61
“Like other E3 ubiquitin ligases, it is a component of the ubiquitin proteasome system (UPS), a main cellular pathway that promotes removal of damaged or misfolded proteins [36], it is involved in signal transduction, protein and membrane trafficking and transcriptional regulation [37–39], replication and transcription…”
BackgroundWang, L., Yang, H., Xia, Y., & Feng, Z. (2010) · APOPTOSIS · doi:10.1007/s10495-010-0547-z · Cited by 62
Wang, X., Feng, S., Wang, Z., Yuan, Y., Chen, N., & Zhang, Y. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00914-2 · Cited by 65
Parkin Is Protective against Proteotoxic Stress in a Transgenic Zebrafish Model
Fett, M. E., Pilsl, A., Paquet, D., van Bebber, F., Haass, C., Tatzelt, J., Schmid, B., & Winklhofer, K. F. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011783 · Cited by 59
“In support of its crucial role in preventing stress-induced cell death, parkin gene expression is transcriptionally upregulated in response to cellular stress [3,16,18,19,20,21,22,23,24,25,26].”
BackgroundParkin in Parkinson’s Disease and Cancer: a Double-Edged Sword
Wahabi, K., Perwez, A., & Rizvi, M. M. A. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0879-1 · Cited by 58
“In the presence of Parkin, ROS formation was consistently reduced in mitochondria [58].”
BackgroundParkin targets NOD2 to regulate astrocyte endoplasmic reticulum stress and inflammation
Singh, K., Han, K., Tilve, S. M., Wu, K., Geller, H. M., & Sack, M. N. (2018) · Glia · doi:10.1002/glia.23482 · Cited by 58
Covalent ISG15 conjugation positively regulates the ubiquitin E3 ligase activity of parkin
Im, E., Yoo, L., Hyun, M., Shin, W. H., & Chung, K. C. (2016) · Open Biology · doi:10.1098/rsob.160193 · Cited by 55
Berg, D. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9346-5 · Cited by 56
“Parkin is important for neuronal survival as it is involved in a number of different neuroprotective roles including protection against cellular inuslts like a-synuclein toxicity [73], or proteasomal dysfunction [74] or confering resistance towards stimuli that promote mitochondria—dependent apoptosis [75] and dopamin…”
BackgroundHam, S., Lee, Y., Jo, M., Kim, H., Kang, H., Jo, A., Lee, G. H., Mo, Y. J., Park, S. C., Lee, Y. S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-00614-w · Cited by 53
PARK2 Mediates Interleukin 6 and Monocyte Chemoattractant Protein 1 Production by Human Macrophages
de Léséleuc, L., Orlova, M., Cobat, A., Girard, M., Hương, N. T., Ba, N. N., Thuc, N. V., Truman, R. W., Spencer, J. S., Adams, L. B., et al. (2013) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002015 · Cited by 52
“Parkin has been given multiple roles related to neuronal survival in the context of Parkinsonism [15–22].”
BackgroundAkhtar, M. W., Sunico, C. R., Nakamura, T., & Lipton, S. A. (2012) · International Journal of Cell Biology · doi:10.1155/2012/463756 · Cited by 55
“The parkin gene encodes an ubiquitin E3 ligase that targets many proteins for proteasomal degradation and also has a neuroprotective role in PD-related apoptotic events [56, 60].”
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
