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Peroxynitrite induces HO-1 expression via PI3K/Akt-dependent activation of NF-E2-related factor 2 in PC12 cells

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dc.contributor.authorLi, Mei-Hua-
dc.contributor.authorCha, Young-Nam-
dc.contributor.authorSurh, Young-Joon-
dc.date.accessioned2021-01-31T09:29:03Z-
dc.date.available2021-01-31T09:29:03Z-
dc.date.issued2006-10-
dc.identifier.citationFree Radical Biology and Medicine, Vol.41 No.7, pp.1079-1091-
dc.identifier.issn0891-5849-
dc.identifier.other3644-
dc.identifier.urihttps://hdl.handle.net/10371/172718-
dc.description.abstractPeroxynitrite is a strong oxidant produced by rapid interaction between superoxide anion and nitric oxide radicals and induces oxidative stress and cell death. Treatment of PC12 cells with 3-morpholinosydnonimine (SIN-1), a generator of peroxynitrite, induced the expression of heme oxygenase-1 (HO-1), an antioxidant cytoprotective enzyme. Inhibition of the HO activity by zinc protoporphyrin IX or knockdown of HO-1 gene expression with siRNA exacerbated the SIN-1-induced apoptosis. After SIN-1 treatment, there was a time-related increase in nuclear localization and subsequent binding of NF-E2-related factor 2 (Nrf2) to the antioxidant-responsive element (ARE). Transfection of PC 12 cells with dominant-negative Nrf2 abolished the SIN-1-induced increase in Nrf2-ARE binding and subsequent upregulation of HO-1 expression, leading to enhanced cell death. Upon exposure of PC12 cells to SIN-1, the phosphatidylinositol 3-kinase (PI3K) activity was increased in a time-dependent manner. Pretreatment of cells with LY294002, a pharmacologic inhibitor of PI3K or transfection with the kinase-dead mutant Akt abrogated the SIN-1-induced Nrf2 activation and HO-1 expression. Taken together, these results suggest that peroxynitrite activates Nrf2 via PI3K/Akt signaling and enhances Nrf2-ARE binding, which leads to upregulation of HO-1 expression. The SIN-1-induced HO-1 upregulation may confer the adaptive survival response against nitrosative stress. (c) 2006 Elsevier Inc. All rights reserved.-
dc.subjectperoxynitrite-
dc.subjectHeme oxygenase-
dc.subjectNF-E2-related factor 2-
dc.subjectantioxidant responsive element-
dc.subjectAkt-
dc.subjectapoptosis-
dc.subjectPC12 cells-
dc.subjectfree radicals-
dc.titlePeroxynitrite induces HO-1 expression via PI3K/Akt-dependent activation of NF-E2-related factor 2 in PC12 cells-
dc.typeArticle-
dc.contributor.AlternativeAuthor서영준-
dc.identifier.doi10.1016/j.freeradbiomed.2006.06.010-
dc.citation.journaltitleFree Radical Biology and Medicine-
dc.identifier.scopusid2-s2.0-33748310792-
dc.citation.endpage1091-
dc.citation.number7-
dc.citation.startpage1079-
dc.citation.volume41-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0891584906004126?via%3Dihub-
dc.identifier.rimsid3644-
dc.identifier.sci000241142100008-
dc.contributor.affiliatedAuthorSurh, Young-Joon-
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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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