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[PMID]: | 27872193 |
[Au] Autor: | Nishina T; Deguchi Y; Miura R; Yamazaki S; Shinkai Y; Kojima Y; Okumura K; Kumagai Y; Nakano H |
[Ad] Endereço: | From the Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540. |
[Ti] Título: | Critical Contribution of Nuclear Factor Erythroid 2-related Factor 2 (NRF2) to Electrophile-induced Interleukin-11 Production. |
[So] Source: | J Biol Chem;292(1):205-216, 2017 Jan 06. | [Is] ISSN: | 1083-351X |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that plays a crucial role in protection of cells from electrophile-induced toxicity through up-regulating phase II detoxifying enzymes and phase III transporters. We previously reported that oxidative stress induces up-regulation of interleukin-11 (IL-11), a member of the IL-6 family that ameliorates acetaminophen-induced liver toxicity. However, a role for IL-11 in protection of cells from electrophile-induced toxicity remains unclear. Here we show that an environmental electrophile, 1,2-naphthoquinone (1,2-NQ), but not 15d-prostaglandin J (PGJ ) or tert-butylhydroxyquinone (tBHQ), induced IL-11 production. Consistent with a crucial role for prolonged ERK activation in H O -induced IL-11 production, 1,2-NQ, but not 15d-PGJ or tBHQ, elicited prolonged ERK activation. Conversely, inhibition of the ERK pathway by a MEK inhibitor completely blocked 1,2-NQ-induced IL-11 production at both protein and mRNA levels, further substantiating an intimate cross-talk between ERK activation and 1,2-NQ-induced IL-11 production. Promoter analysis of the Il11 gene revealed that two AP-1 sites were essential for 1,2-NQ-induced promoter activities. Among various members of the AP-1 family, Fra-1 was up-regulated by 1,2-NQ, and its up-regulation was blocked by a MEK inhibitor. Although NRF2 was not required for H O -induced IL11 up-regulation, NRF2 was essential for 1,2-NQ-induced IL11 up-regulation by increasing Fra-1 proteins possibly through promoting mRNA translation of FOSL1 Finally, intraperitoneal administration of 1,2-NQ induced body weight loss in wild-type mice, which was further exacerbated in Il11ra1 mice compared with Il11ra1 mice. Together, both Fra-1 and NRF2 play crucial roles in IL-11 production that protects cells from 1,2-NQ intestinal toxicity. |
[Mh] Termos MeSH primário: |
Interleucina-11/biossíntese Enteropatias/prevenção & controle Fator 2 Relacionado a NF-E2/metabolismo Naftoquinonas/toxicidade Peritonite/prevenção & controle Prostaglandina D2/análogos & derivados
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[Mh] Termos MeSH secundário: |
Animais Antineoplásicos/toxicidade Células Cultivadas Regulação da Expressão Gênica/efeitos dos fármacos Células HEK293 Células Hep G2 Seres Humanos Peróxido de Hidrogênio/farmacologia Subunidade alfa de Receptor de Interleucina-11/fisiologia Enteropatias/induzido quimicamente Enteropatias/metabolismo Enteropatias/patologia Sistema de Sinalização das MAP Quinases Camundongos Camundongos Endogâmicos C57BL Camundongos Knockout Fator 2 Relacionado a NF-E2/genética Oxidantes/farmacologia Estresse Oxidativo/efeitos dos fármacos Peritonite/induzido quimicamente Peritonite/metabolismo Peritonite/patologia Prostaglandina D2/toxicidade Espécies Reativas de Oxigênio/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (15-deoxyprostaglandin J2); 0 (Antineoplastic Agents); 0 (Il11ra1 protein, mouse); 0 (Interleukin-11); 0 (Interleukin-11 Receptor alpha Subunit); 0 (NF-E2-Related Factor 2); 0 (Naphthoquinones); 0 (Oxidants); 0 (Reactive Oxygen Species); 60203-57-8 (9-deoxy-delta-9-prostaglandin D2); 804K62F61Q (1,2-naphthoquinone); BBX060AN9V (Hydrogen Peroxide); RXY07S6CZ2 (Prostaglandin D2) |
[Em] Mês de entrada: | 1706 |
[Cu] Atualização por classe: | 170602 |
[Lr] Data última revisão:
| 170602 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 161123 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1074/jbc.M116.744755 |
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