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4-Hydroxyestradiol induces oxidative stress and apoptosis in human mammary epithelial cells: possible protection by NF-κB and ERK/MAPK : 4-Hydroxyestradiol induces oxidative stress and apoptosis in human mammary epithelial cells: Possible protection by NF-kappa B and ERK/MAPK
DC Field | Value | Language |
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dc.contributor.author | Chen, Zhi-Hua | - |
dc.contributor.author | Na, Hye-Kyung | - |
dc.contributor.author | Hurh, Yeon-Jin | - |
dc.contributor.author | Surh, Young-Joon | - |
dc.date.accessioned | 2021-01-31T10:24:58Z | - |
dc.date.available | 2021-01-31T10:24:58Z | - |
dc.date.created | 2017-11-15 | - |
dc.date.issued | 2005-10 | - |
dc.identifier.citation | Toxicology and Applied Pharmacology, Vol.208 No.1, pp.46-56 | - |
dc.identifier.issn | 0041-008X | - |
dc.identifier.other | 3892 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172912 | - |
dc.description.abstract | Catechol estrogens, the hydroxylated metabolites of 17 beta-estradiol (E-2) have been considered to be implicated in estrogen-induced carcinogenesis. 4-Hydroxyestradiot (4-OHE2), an oxidized metabolite of E-2 formed preferentially by cytochrome P450 1B1, reacts with DNA to form depurinating adducts thereby exerting genotoxicity and carcinogenicity. 4-OHE2 undergoes 2-electron oxidation to quinone via semiquinone, and during this process, reactive oxygen species (ROS) can be generated to cause DNA damage and cell death. In the present study, 4-OHE2 was found to elicit cytotoxicity in cultured human mammary epithelial (MCF-10A) cells, which was blocked by the antioxidant trolox. MCF-10A cells treated with 4-OHE2 exhibited increased intracellular ROS accumulation and 8-oxo-7,8-dihydroxy-2'-deoxyguanosine formation, and underwent apoptosis as determined by poly(ADP-ribose)polymerase cleavage and disruption of mitochondrial transmembrane potential. The redox-sensitive transcription factor nuclear factor kappa B (NF-kappa B) was transiently activated by 4-OHE2 treatment. Cotreatment of MCF-10A cells with the NF-kappa B inhibitor, L-1-tosylamido-2-phenylethyl chloromethyl ketone, exacerbated 4-OHE2-induced cell death. 4-OHE2 also caused transient activation of extracellular signal-regulated protein kinases (ERK) involved in transmitting cell survival or death signals. A pharmacological inhibitor of ERK aggravated the 4-OHE2-induced cytotoxicity, supporting the pivotal role of ERK in protecting against catechol estrogen-induced oxidative cell death. (c) 2005 Elsevier Inc. All rights reserved. | - |
dc.language | 영어 | - |
dc.publisher | Academic Press | - |
dc.title | 4-Hydroxyestradiol induces oxidative stress and apoptosis in human mammary epithelial cells: possible protection by NF-κB and ERK/MAPK | - |
dc.title.alternative | 4-Hydroxyestradiol induces oxidative stress and apoptosis in human mammary epithelial cells: Possible protection by NF-kappa B and ERK/MAPK | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 서영준 | - |
dc.identifier.doi | 10.1016/j.taap.2005.01.010 | - |
dc.citation.journaltitle | Toxicology and Applied Pharmacology | - |
dc.identifier.wosid | 000232476800005 | - |
dc.identifier.scopusid | 2-s2.0-24744454832 | - |
dc.citation.endpage | 56 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 46 | - |
dc.citation.volume | 208 | - |
dc.identifier.sci | 000232476800005 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Surh, Young-Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | PAH-O-QUINONES | - |
dc.subject.keywordPlus | DNA-DAMAGE | - |
dc.subject.keywordPlus | ESTROGEN METABOLISM | - |
dc.subject.keywordPlus | CATECHOL ESTROGENS | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | ESTRADIOL | - |
dc.subject.keywordPlus | COPPER | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordPlus | ANTIOXIDANT | - |
dc.subject.keywordPlus | GENERATION | - |
dc.subject.keywordAuthor | 4-OHE2 | - |
dc.subject.keywordAuthor | ROS | - |
dc.subject.keywordAuthor | oxidative DNA damage | - |
dc.subject.keywordAuthor | apoptosis | - |
dc.subject.keywordAuthor | NF-kappa B | - |
dc.subject.keywordAuthor | ERK | - |
dc.subject.keywordAuthor | MCF-10A cells | - |
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