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17-Oxo-docosahexaenoic acid induces Nrf2-mediated expression of heme oxygenase-1 in mouse skin in vivo and in cultured murine epidermal cells

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dc.contributor.authorJamil, Muhammad Usman-
dc.contributor.authorKim, Jimin-
dc.contributor.authorYum, Hye-Won-
dc.contributor.authorKim, Seong Hoon-
dc.contributor.authorKim, Su-Jung-
dc.contributor.authorKim, Do-Hee-
dc.contributor.authorCho, Nam-Chul-
dc.contributor.authorNa, Hye-Kyung-
dc.contributor.authorSurh, Young-Joon-
dc.date.accessioned2021-01-31T09:19:19Z-
dc.date.available2021-01-31T09:19:19Z-
dc.date.issued2020-01-
dc.identifier.citationArchives of Biochemistry and Biophysics, Vol.679, p. 108156-
dc.identifier.issn0003-9861-
dc.identifier.other94849-
dc.identifier.urihttps://hdl.handle.net/10371/172569-
dc.description.abstractRecently, growing attention has been given to new classes of bioactive lipid mediators derived from omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), especially in the context of their role as endogenous signal modulators. One such molecule is 17-oxo-DHA, generated from DHA by the action of COX2 and a dehydrogenase. The redox-sensitive transcription factor, Nrf2 plays a key role in cellular stress responses. In the present study, the effects of 17-oxo-DHA on Nrf2-mediated expression of cytoprotective enzymes were examined in mouse skin in vivo and cultured murine epidermal JB6 cells. Topical application of 17-oxo-DHA markedly elevated the nuclear localization of Nrf2 and expression of heme oxygenase-1 (HO-1) and NAD(P) H:quinone oxidoreductase-1 in hairless mouse skin. In contrast to 17-oxo-DHA, the non-electrophilic metabolic precursor 17-hydroxy-DHA was a much weaker inducer of Nrf2 activation and its target protein expression. Likewise, 17-oxo-DHA significantly enhanced nuclear translocation and transcriptional activity of Nrf2 with concomitant upregulation of HO-1 expression in cultured JB6 cells. 17-Oxo-DHA was a much stronger inducer of Nrf2-mediated antioxidant response than its parent molecule, DHA. HO-1 expression was abolished in Nrf2 knockdown JB6 cells or embryo fibroblasts from Nrf2 knock out mice. 17-Oxo-DHA also markedly reduced the level of Keap1 protein by inducing ubiquitination. Mutation of Cys151 and Cys273 in Keap1 abrogated 17-oxo-DHA-induced ubiquitination and proteasome-mediated degradation of Keap1 as well as HO-1 expression, suggesting that these cysteine residues are putative sites for 17-oxo-DHA binding. Further, Keap1 degradation stimulated by 17-oxo-DHA coincided with accumulation of the autophagy substrate, p62/SQSTM1.-
dc.subjectDocosahexaenoic acid-
dc.subjectHeme oxygenase-1-
dc.subjectMouse skin-
dc.subjectNrf2-
dc.subjectOmega-3 polyunsaturated fatty acids-
dc.subject17-Oxo-DHA-
dc.title17-Oxo-docosahexaenoic acid induces Nrf2-mediated expression of heme oxygenase-1 in mouse skin in vivo and in cultured murine epidermal cells-
dc.typeArticle-
dc.contributor.AlternativeAuthor서영준-
dc.identifier.doi10.1016/j.abb.2019.108156-
dc.citation.journaltitleArchives of Biochemistry and Biophysics-
dc.identifier.scopusid2-s2.0-85076201276-
dc.citation.startpage108156-
dc.citation.volume679-
dc.identifier.rimsid94849-
dc.identifier.sci000525443900001-
dc.description.isOpenAccessY-
dc.contributor.affiliatedAuthorSurh, Young-Joon-
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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