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15-Deoxy-Delta(12,14)-prostaglandin J(2) stabilizes hypoxia inducible factor-1 alpha through induction of heme oxygenase-1 and direct modification ofprolyl-4-hydroxylase 2
DC Field | Value | Language |
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dc.contributor.author | Choi, Jee-Eun | - |
dc.contributor.author | Kim, Jung-Hyun | - |
dc.contributor.author | Song, Na-Young | - |
dc.contributor.author | Suh, Jinyoung | - |
dc.contributor.author | Kim, Do-Hee | - |
dc.contributor.author | Kim, Su-Jung | - |
dc.contributor.author | Na, Hye-Kyung | - |
dc.contributor.author | Nadas, Janos | - |
dc.contributor.author | Dong, Zigang | - |
dc.contributor.author | Cha, Young-Nam | - |
dc.contributor.author | Surh, Young-Joon | - |
dc.date.accessioned | 2021-01-31T10:13:41Z | - |
dc.date.available | 2021-01-31T10:13:41Z | - |
dc.date.created | 2018-09-07 | - |
dc.date.issued | 2016-10 | - |
dc.identifier.citation | Free Radical Research, Vol.50 No.10, pp.1140-1152 | - |
dc.identifier.issn | 1071-5762 | - |
dc.identifier.other | 51995 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172741 | - |
dc.description.abstract | 15-Deoxy-(12,14)-prostaglandin J(2) (15d-PGJ(2)), a representative J-series cyclopentenone prostaglandin, has biphasic roles in cell proliferation and apoptosis. Hypoxia inducible factor-1 (HIF-1) regulates expression of various genes involved in tumor growth and angiogenesis. In the present study, treatment of human breast cancer (MCF-7) cells with 15d-PGJ(2) resulted in the accumulation of the -subunit of HIF-1. Pretreatment with zinc protoporphyrin IX, a pharmacological inhibitor of heme oxygenase-1 (HO-1), as well as siRNA knockdown of HO-1 gene in MCF-7 cells attenuated 15d-PGJ(2)-mediated HIF-1 accumulation. 15d-PGJ(2) treatment increased intracellular production of reactive oxygen species (ROS), which was mediated by HO-1 induction. Preincubation of MCF-7 cells with trolox, a water-soluble form of vitamin E, attenuated 15d-PGJ(2)-induced HIF-1 expression although HO-1 expression was unchanged. This finding suggests that ROS accumulated as a consequence of HO-1 up-regulation can enhance HIF-1 expression in MCF-7 cells treated with 15d-PGJ(2). Alternatively, 15d-PGJ(2) was found to covalently bind to HIF-1 prolyl-4-hydroxylase 2 (PHD2) in MCF-7 cells, which hampers the proline hydroxylation of HIF-1, thereby disrupting ubiquitin-dependent proteasomal degradation of this transcription factor. Pretreatment with thiol reducing agents blunted 15d-PGJ(2)-induced HIF-1 stabilization, indicative of a cysteine residue as a direct target of 15d-PGJ(2). Molecular docking analysis suggests that 15d-PGJ(2) preferentially binds to PHD2 in the vicinity of the Cys(201) residue based on binding energies and carbon-sulfur distances. In summary, 15d-PGJ(2) stabilizes HIF-1 in MCF-7 cells through HO-1 induction with subsequent ROS generation and also through direct modification of PHD2. | - |
dc.language | 영어 | - |
dc.publisher | Taylor & Francis | - |
dc.title | 15-Deoxy-Delta(12,14)-prostaglandin J(2) stabilizes hypoxia inducible factor-1 alpha through induction of heme oxygenase-1 and direct modification ofprolyl-4-hydroxylase 2 | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 서영준 | - |
dc.identifier.doi | 10.1080/10715762.2016.1219352 | - |
dc.citation.journaltitle | Free Radical Research | - |
dc.identifier.wosid | 000387922000011 | - |
dc.identifier.scopusid | 2-s2.0-84986205320 | - |
dc.citation.endpage | 1152 | - |
dc.citation.number | 10 | - |
dc.citation.startpage | 1140 | - |
dc.citation.volume | 50 | - |
dc.identifier.sci | 000387922000011 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Surh, Young-Joon | - |
dc.type.docType | Article; Proceedings Paper | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | BREAST-CANCER CELLS | - |
dc.subject.keywordPlus | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR PROTEIN | - |
dc.subject.keywordPlus | PROLYL HYDROXYLASE | - |
dc.subject.keywordPlus | FACTOR PROLYL-4-HYDROXYLASE | - |
dc.subject.keywordPlus | HIF-ALPHA | - |
dc.subject.keywordPlus | PROLINE HYDROXYLATION | - |
dc.subject.keywordPlus | COX-2 EXPRESSION | - |
dc.subject.keywordPlus | CARBON-MONOXIDE | - |
dc.subject.keywordPlus | DNA-BINDING | - |
dc.subject.keywordAuthor | 15-Deoxy-Delta(12,14)-prostaglandin J(2) | - |
dc.subject.keywordAuthor | hypoxia inducible factor-1 alpha | - |
dc.subject.keywordAuthor | heme oxygenase-1 | - |
dc.subject.keywordAuthor | prolyl-4-hydroxylase 2 | - |
dc.subject.keywordAuthor | MCF-7 cells | - |
dc.subject.keywordAuthor | cyclopentenone prostaglandin | - |
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