S-nitrosylated PARIS Leads to the Sequestration of PGC-1α into Insoluble Deposits in Parkinson’s Disease Model
DC Field | Value | Language |
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dc.contributor.author | Kim, H.[Kim, H.] | - |
dc.contributor.author | Lee, J.-Y.[Lee, J.-Y.] | - |
dc.contributor.author | Park, S.J.[Park, S.J.] | - |
dc.contributor.author | Kwag, E.[Kwag, E.] | - |
dc.contributor.author | Kim, J.[Kim, J.] | - |
dc.contributor.author | Shin, J.-H.[Shin, J.-H.] | - |
dc.date.accessioned | 2023-05-18T17:42:46Z | - |
dc.date.available | 2023-05-18T17:42:46Z | - |
dc.date.created | 2023-05-18 | - |
dc.date.issued | 2022-11 | - |
dc.identifier.issn | 2073-4409 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/105749 | - |
dc.description.abstract | Neuronal accumulation of parkin-interacting substrate (PARIS), a transcriptional repressor of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), has been observed in Parkinson’s disease (PD). Herein, we showed that PARIS can be S-nitrosylated at cysteine 265 (C265), and S-nitrosylated PARIS (SNO-PARIS) translocates to the insoluble fraction, leading to the sequestration of PGC-1α into insoluble deposits. The mislocalization of PGC-1α in the insoluble fraction was observed in S-nitrosocysteine-treated PARIS knockout (KO) cells overexpressing PARIS WT but not S-nitrosylation deficient C265S mutant, indicating that insolubility of PGC-1α is SNO-PARIS-dependent. In the sporadic PD model, α-synuclein preformed fibrils (α-syn PFFs)-injected mice, we found an increase in PARIS, SNO-PARIS, and insoluble sequestration of PGC-1α in substantia nigra (SN), resulting in the reduction of mitochondrial DNA copy number and ATP concentration that were restored by N(ω)-nitro-L-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor. To assess the dopaminergic (DA) neuronal toxicity by SNO-PARIS, lentiviral PARIS WT, C265S, and S-nitrosylation mimic C265W was injected into the SN of either PBS- or α-syn PFFs-injected mice. PARIS WT and C265S caused DA neuronal death to a comparable extent, whereas C265W caused more severe DA neuronal loss in PBS-injected mice. Interestingly, there was synergistic DA loss in both lenti-PARIS WT and α-syn PFFs-injected mice, indicating that SNO-PARIS by α-syn PFFs contributes to the DA toxicity in vivo. Moreover, α-syn PFFs-mediated increment of PARIS, SNO-PARIS, DA toxicity, and behavioral deficits were completely nullified in neuronal NOS KO mice, suggesting that modulation of NO can be a therapeutic for α-syn PFFs-mediated neurodegeneration. © 2022 by the authors. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.title | S-nitrosylated PARIS Leads to the Sequestration of PGC-1α into Insoluble Deposits in Parkinson’s Disease Model | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, H.[Kim, H.] | - |
dc.contributor.affiliatedAuthor | Kim, J.[Kim, J.] | - |
dc.contributor.affiliatedAuthor | Shin, J.-H.[Shin, J.-H.] | - |
dc.identifier.doi | 10.3390/cells11223682 | - |
dc.identifier.scopusid | 2-s2.0-85142442986 | - |
dc.identifier.wosid | 000887106900001 | - |
dc.identifier.bibliographicCitation | Cells, v.11, no.22 | - |
dc.relation.isPartOf | Cells | - |
dc.citation.title | Cells | - |
dc.citation.volume | 11 | - |
dc.citation.number | 22 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | NITRIC-OXIDE | - |
dc.subject.keywordPlus | PROMOTES | - |
dc.subject.keywordPlus | NEURODEGENERATION | - |
dc.subject.keywordPlus | UBIQUITINATION | - |
dc.subject.keywordPlus | DYSFUNCTION | - |
dc.subject.keywordAuthor | nitrosative stress | - |
dc.subject.keywordAuthor | PARIS/ZNF746 | - |
dc.subject.keywordAuthor | Parkinson’s disease | - |
dc.subject.keywordAuthor | PGC-1α | - |
dc.subject.keywordAuthor | S-nitrosylation | - |
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