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| [PMID]: | 29217191 |
| [Au] Autor: | Yoshida K; Nakai A; Kaneshiro K; Hashimoto N; Suzuki K; Uchida K; Hashimoto T; Kawasaki Y; Tateishi K; Nakagawa N; Shibanuma N; Sakai Y; Hashiramoto A |
| [Ad] Endereço: | Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan. |
| [Ti] Título: | TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells. |
| [So] Source: | Biochem Biophys Res Commun;495(2):1675-1680, 2018 01 08. | | [Is] ISSN: | 1090-2104 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Tumor necrosis factor (TNF)-α is responsible for expressions of several clock genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal fluctuation. We tried to determine the mechanism involved in over-expression of Bmal1, induced by TNF-α, in primary cultured rheumatoid synovial cells. Cells were incubated with intra-cellular Ca chelator BAPTA-AM, calcineurin inhibitor FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or transfected with p300 and CBP small interfering RNA (siRNA) before stimulation with TNF-α. Oscillation phase and amplitude of Bmal1, transcriptional activator Rorα, transcriptional repressor Rev-erbα, and histone acetyltransferases (p300 and Cbp) were evaluated by quantitative real-time PCR. As results, TNF-α did not influence the oscillation phase of Rev-erbα, while enhanced those of Rorα, resulting in over-expression of Bmal1. When Ca influx was inhibited by BAPTA-AM, TNF-α-mediated up-regulation of Rorα was cancelled, however, that of Bmal1 was still apparent. When we further explored another pathway between TNF-α and Bmal1, TNF-α suppressed the expression of Rev-erbα in the absence of Ca influx, as well as those of p300 and Cbp genes. Finally, actions of TNF-α, in increasing Bmal1/Rorα and decreasing Rev-erbα, were cancelled by C646 treatment or silencing of both p300 and Cbp. In conclusion, we determined a novel role of TNF-α in inducing Bmal1 via dual calcium dependent pathways; Rorα was up-regulated in the presence of Ca influx and Rev-erbα was down-regulated in the absence of that. Results proposed that inhibition of p300/CBP could be new therapeutic targets for RA. |
| [Mh] Termos MeSH primário: |
Fatores de Transcrição ARNTL/genética
Artrite Reumatoide/genética
Artrite Reumatoide/metabolismo
Sinalização do Cálcio
Relógios Circadianos/genética
Membrana Sinovial/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
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| [Mh] Termos MeSH secundário: |
Artrite Reumatoide/patologia
Benzoatos/farmacologia
Proteína de Ligação a CREB/antagonistas & inibidores
Proteína de Ligação a CREB/genética
Quelantes de Cálcio/farmacologia
Sinalização do Cálcio/efeitos dos fármacos
Células Cultivadas
Proteína p300 Associada a E1A/antagonistas & inibidores
Proteína p300 Associada a E1A/genética
Ácido Egtázico/análogos & derivados
Ácido Egtázico/farmacologia
Expressão Gênica/efeitos dos fármacos
Seres Humanos
Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética
Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética
Pirazóis/farmacologia
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
RNA Interferente Pequeno/genética
Membrana Sinovial/efeitos dos fármacos
Membrana Sinovial/patologia
Fator de Necrose Tumoral alfa/farmacologia
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (ARNTL Transcription Factors); 0 (ARNTL protein, human); 0 (Benzoates); 0 (C646 compound); 0 (Calcium Chelating Agents); 0 (NR1D1 protein, human); 0 (Nuclear Receptor Subfamily 1, Group D, Member 1); 0 (Nuclear Receptor Subfamily 1, Group F, Member 1); 0 (Pyrazoles); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 0 (RORA protein, human); 0 (Tumor Necrosis Factor-alpha); 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester); 526U7A2651 (Egtazic Acid); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (CREBBP protein, human); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human) |
| [Em] Mês de entrada: | 1802 |
| [Cu] Atualização por classe: | 180220 |
[Lr] Data última revisão:
| 180220 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 171209 |
| [St] Status: | MEDLINE |
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