PKC delta-dependent p47phox activation mediates methamphetamine-induced dopaminergic neurotoxicity
DC Field | Value | Language |
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dc.contributor.author | Duy-Khanh Dang | - |
dc.contributor.author | Shin, Eun-Joo | - |
dc.contributor.author | Kim, Dae-Joong | - |
dc.contributor.author | Hai-Quyen Tran | - |
dc.contributor.author | Jeong, Ji Hoon | - |
dc.contributor.author | Jang, Choon-Gon | - |
dc.contributor.author | Ottersen, Ole Petter | - |
dc.contributor.author | Nah, Seung-Yeol | - |
dc.contributor.author | Hong, Jau-Shyong | - |
dc.contributor.author | Nabeshima, Toshitaka | - |
dc.contributor.author | Kim, Hyoung-Chun | - |
dc.date.available | 2019-01-22T14:08:13Z | - |
dc.date.issued | 2018-02 | - |
dc.identifier.issn | 0891-5849 | - |
dc.identifier.issn | 1873-4596 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/1198 | - |
dc.description.abstract | Protein kinase C (PKC) has been recognized to activate NADPH oxidase (PHOX). However, the interaction between PKC and PHOX in vivo remains elusive. Treatment with methamphetamine (MA) resulted in a selective increase in PKC delta expression out of PKC isoforms. PKC delta co-immunoprecipitated with p47phox, and facilitated phosphorylation and membrane translocation of p47phox. MA-induced increases in PHOX activity and reactive oxygen species were attenuated by knockout of p47phox or PKC delta. In addition, MA-induced impairments in the Nrf-2-related glutathione synthetic system were also mitigated by knockout of p47phox or PKC delta. Glutathione-immunoreactivity was co-localized in Iba-1-labeled microglial cells and in NeuN-labeled neurons, but not in GFAP-labeled astrocytes, reflecting the necessity for self-protection against oxidative stress by mainly microglia. Buthionine-sulfoximine, an inhibitor of glutathione biosynthesis, potentiated microglial activation and proapoptotic changes, leading to dopaminergic losses. These neurotoxic processes were attenuated by rottlerin, a pharmacological inhibitor of PKC delta, genetic inhibitions of PKC delta [ i.e., PKC delta knockout mice (KO) and PKC delta antisense oligonucleotide (ASO)], or genetic inhibition of p47phox (i.e., p47phox KO or p47phox ASO). Rottlerin did not exhibit any additive effects against the protective activity offered by genetic inhibition of p47phox. Therefore, we suggest that PKC delta is a critical regulator for p47phox activation induced by MA, and that Nrf-2-dependent GSH induction via inhibition of PKC delta or p47phox, is important for dopaminergic protection against MA insult. | - |
dc.format.extent | 20 | - |
dc.publisher | ELSEVIER SCIENCE INC | - |
dc.title | PKC delta-dependent p47phox activation mediates methamphetamine-induced dopaminergic neurotoxicity | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.freeradbiomed.2017.12.018 | - |
dc.identifier.bibliographicCitation | FREE RADICAL BIOLOGY AND MEDICINE, v.115, pp 318 - 337 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000419709200029 | - |
dc.identifier.scopusid | 2-s2.0-85038821090 | - |
dc.citation.endPage | 337 | - |
dc.citation.startPage | 318 | - |
dc.citation.title | FREE RADICAL BIOLOGY AND MEDICINE | - |
dc.citation.volume | 115 | - |
dc.type.docType | Article | - |
dc.publisher.location | 네델란드 | - |
dc.subject.keywordAuthor | Methamphetamine | - |
dc.subject.keywordAuthor | Dopamine | - |
dc.subject.keywordAuthor | Striatum | - |
dc.subject.keywordAuthor | PKC delta knockout mice | - |
dc.subject.keywordAuthor | PKCd antisense oligonucleotide | - |
dc.subject.keywordAuthor | p47phox knockout mice | - |
dc.subject.keywordAuthor | 47phox antisense oligonucleotide | - |
dc.subject.keywordAuthor | Nrf2-transcription factor | - |
dc.subject.keywordAuthor | Glutathione-immunoreactivity | - |
dc.subject.keywordAuthor | Microglia | - |
dc.subject.keywordAuthor | Pro-apoptosis | - |
dc.subject.keywordPlus | PROTEIN-KINASE-C | - |
dc.subject.keywordPlus | MICROGLIAL NADPH OXIDASE | - |
dc.subject.keywordPlus | IDIOPATHIC PARKINSONS-DISEASE | - |
dc.subject.keywordPlus | L-BUTHIONINE SULFOXIMINE | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | NEURODEGENERATIVE DISEASES | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | BRAIN GLUTATHIONE | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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