DC Field | Value | Language |
---|---|---|
dc.contributor.author | An, Hyun-Jung | ko |
dc.contributor.author | Maeng, Oky | ko |
dc.contributor.author | Kang, Kyoung-Hee | ko |
dc.contributor.author | Lee, Jie-Oh | ko |
dc.contributor.author | Kim, Young-Sang | ko |
dc.contributor.author | Paik, Sang-Gi | ko |
dc.contributor.author | Lee, Hayyoung | ko |
dc.date.accessioned | 2009-09-24T04:57:14Z | - |
dc.date.available | 2009-09-24T04:57:14Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2006-11 | - |
dc.identifier.citation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.281, no.45, pp.33939 - 33948 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10203/11485 | - |
dc.description.abstract | Nitric oxide ( NO) produced by NO synthases causes nitration and nitrosylation of cellular factors. We have shown previously that endogenously produced or exogenously added NO induces expression of BNIP3 (Bcl-2/adenovirus E1B 19kDa-interacting protein 3), leading to death of macrophages (Yook, Y.-H., Kang, K.-H., Maeng, O., Kim, T.-R., Lee, J.-O., Kang, K.-i., Kim, Y.-S., Paik, S.-G., and Lee, H. ( 2004) Biochem. Biophys. Res. Commun. 321, 298-305). We now provide evidence that Ras mediates NO-induced BNIP3 expression via the MEK/ERK/hypoxia-inducible factor (HIF)-1 pathway. (a)ras-Q61L, a constitutively active form of Ras, up-regulated BNIP3 protein expression by enhancing Bnip3 promoter activity, and ras-S17N, a dominant-negative form, and ras-C118S, an S-nitrosylation mutant, blocked NO-induced BNIP3 expression, suggesting that Ras acts downstream of NO and that NO activates Ras by nitrosylation. (b) U0126, a specific MEK inhibitor, completely abolished BNIP3 expression and the stimulation of promoter activity by NO and Ras, whereas 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one, SB203580, and wortmannin, specific inhibitors of soluble guanylyl cyclase, p38 MAPK, and phosphatidylinositol 3-kinase, respectively, had no effect. Ras, MEK1/2, and ERK1/2 were sequentially activated by NO treatment of macrophages. ( c) Mutation of the HIF-1-binding site (hypoxia-response element) in the Bnip3 promoter abolished BNIP3 induction, and HIF-1 alpha was strongly induced by NO. (d) Transient expression of activated Ras promoted macrophage death, as did NO, and this Ras-mediated cell death was inhibited by silencing BNIP3 expression. These results suggest that NO-induced death of macrophages is mediated, at least in part, by BNIP3 induction. | - |
dc.description.sponsorship | We thank Selina Chen-Kiang for critical review of the manuscript and Sung-Kyu Ju and the staff at the Korea Basic Science Institute for technical assistance. | en |
dc.language | English | - |
dc.language.iso | en_US | en |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | MITOCHONDRIAL PERMEABILITY TRANSITION | - |
dc.subject | GUANINE-NUCLEOTIDE EXCHANGE | - |
dc.subject | C-HA-RAS | - |
dc.subject | PROTEIN BNIP3 | - |
dc.subject | SURVIVAL RESPONSIVENESS | - |
dc.subject | PANCREATIC-CANCER | - |
dc.subject | GENE-EXPRESSION | - |
dc.subject | BH3 DOMAIN | - |
dc.subject | MACROPHAGES | - |
dc.subject | HYPOXIA | - |
dc.title | Activation of Ras up-regulates pro-apoptotic BNIP3 in nitric oxide-induced cell death | - |
dc.type | Article | - |
dc.identifier.wosid | 000241767600015 | - |
dc.identifier.scopusid | 2-s2.0-33845920075 | - |
dc.type.rims | ART | - |
dc.citation.volume | 281 | - |
dc.citation.issue | 45 | - |
dc.citation.beginningpage | 33939 | - |
dc.citation.endingpage | 33948 | - |
dc.citation.publicationname | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.identifier.doi | 10.1074/jbc.M605819200 | - |
dc.embargo.liftdate | 9999-12-31 | - |
dc.embargo.terms | 9999-12-31 | - |
dc.contributor.localauthor | Lee, Jie-Oh | - |
dc.contributor.nonIdAuthor | An, Hyun-Jung | - |
dc.contributor.nonIdAuthor | Maeng, Oky | - |
dc.contributor.nonIdAuthor | Kang, Kyoung-Hee | - |
dc.contributor.nonIdAuthor | Kim, Young-Sang | - |
dc.contributor.nonIdAuthor | Paik, Sang-Gi | - |
dc.contributor.nonIdAuthor | Lee, Hayyoung | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | MITOCHONDRIAL PERMEABILITY TRANSITION | - |
dc.subject.keywordPlus | GUANINE-NUCLEOTIDE EXCHANGE | - |
dc.subject.keywordPlus | C-HA-RAS | - |
dc.subject.keywordPlus | PROTEIN BNIP3 | - |
dc.subject.keywordPlus | SURVIVAL RESPONSIVENESS | - |
dc.subject.keywordPlus | PANCREATIC-CANCER | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | BH3 DOMAIN | - |
dc.subject.keywordPlus | MACROPHAGES | - |
dc.subject.keywordPlus | HYPOXIA | - |
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