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Curcumin induces stabilization of Nrf2 protein through Keap1 cysteine modification
DC Field | Value | Language |
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dc.contributor.author | Shin, Jun Wan | - |
dc.contributor.author | Chun, Kyung-Soo | - |
dc.contributor.author | Kim, Do-Hee | - |
dc.contributor.author | Kim, Su-Jung | - |
dc.contributor.author | Kim, Seong Hoon | - |
dc.contributor.author | Cho, Nam-Chul | - |
dc.contributor.author | Na, Hye-Kyung | - |
dc.contributor.author | Surh, Young-Joon | - |
dc.date.accessioned | 2021-01-31T09:20:48Z | - |
dc.date.available | 2021-01-31T09:20:48Z | - |
dc.date.created | 2020-05-19 | - |
dc.date.created | 2020-05-19 | - |
dc.date.issued | 2020-03 | - |
dc.identifier.citation | Biochemical Pharmacology, Vol.173, p. 113820 | - |
dc.identifier.issn | 0006-2952 | - |
dc.identifier.other | 100692 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172590 | - |
dc.description.abstract | The present study was aimed to investigate the effects of curcumin, a representative chemopreventive phytochemical with pronounced antioxidant and anti-inflammatory properties, on activation of Nrf2 and expression of its target protein heme oxygenase-1 (HO-1) in mouse skin in vivo and in cultured murine epidermal cells. Treatment of mouse epidermal JB6 cells with curcumin resulted in the induction of HO-1 expression, and this was abrogated in cells transiently transfected with Nrf2 siRNA. While curcumin treatment increased protein expression of Nrf2, it did not alter the steady-state level of the Nrf2 mRNA transcript. Treatment of cells with curcumin stabilized Nrf2 by inhibiting ubiquitination and subsequent 26S proteasomal degradation of this transcription factor. Tetrahydrocurcumin, a non-electrophilic analogue of curcumin that lacks the alpha,beta-unsaturated carbonyl group, failed to induce HO-1 expression as well as nuclear translocation of Nrf2 and its binding to the antioxidant/electrophile response elements. Cells transfected with a mutant Keap1 protein in which cysteine 151 (Cys151) is replaced by serine exhibited marked reduction in curcumin-induced Nrf2 transactivation. Mass spectrometric analysis revealed that curcumin binds to Keap1 Cys151, supporting that this amino acid is a critical target for curcumin modification of Keap1, which facilitates the liberation of Nrf2. Thus, it is likely that the alpha,beta-unsaturated carbonyl moiety of curcumin is essential for its binding to Keap1 and stabilization of Nrf2 by hampering ubiquitination and proteasomal degradation. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier BV | - |
dc.title | Curcumin induces stabilization of Nrf2 protein through Keap1 cysteine modification | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 서영준 | - |
dc.identifier.doi | 10.1016/j.bcp.2020.113820 | - |
dc.citation.journaltitle | Biochemical Pharmacology | - |
dc.identifier.wosid | 000527341300023 | - |
dc.identifier.scopusid | 2-s2.0-85078724725 | - |
dc.citation.startpage | 113820 | - |
dc.citation.volume | 173 | - |
dc.identifier.sci | 000527341300023 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Surh, Young-Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | CUL3-BASED E3 LIGASE | - |
dc.subject.keywordPlus | KINASE-C | - |
dc.subject.keywordPlus | HEME OXYGENASE-1 | - |
dc.subject.keywordPlus | MOUSE SKIN | - |
dc.subject.keywordPlus | ANTIOXIDANT | - |
dc.subject.keywordPlus | UBIQUITINATION | - |
dc.subject.keywordPlus | ADAPTER | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | INDUCTION | - |
dc.subject.keywordAuthor | Curcumin | - |
dc.subject.keywordAuthor | Chemoprevention | - |
dc.subject.keywordAuthor | Nrf2 | - |
dc.subject.keywordAuthor | Keap1 | - |
dc.subject.keywordAuthor | Heme oxygenase | - |
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