論文 - 詳細
| RRC ID | 38460 |
|---|---|
| 著者 | Yoshimura K, Miyamoto Y, Yasuhara R, Maruyama T, Akiyama T, Yamada A, Takami M, Suzawa T, Tsunawaki S, Tachikawa T, Baba K, Kamijo R. |
| タイトル | Monocarboxylate transporter-1 is required for cell death in mouse chondrocytic ATDC5 cells exposed to interleukin-1beta via late phase activation of nuclear factor kappaB and expression of phagocyte-type NADPH oxidase. |
| ジャーナル | J Biol Chem |
| Abstract |
Interleukin-1β (IL-1β) induces cell death in chondrocytes in a nitric oxide (NO)- and reactive oxygen species (ROS)-dependent manner. In this study, increased production of lactate was observed in IL-1β-treated mouse chondrocytic ATDC5 cells prior to the onset of their death. IL-1β-induced cell death in ATDC5 cells was suppressed by introducing an siRNA for monocarboxylate transporter-1 (MCT-1), a lactate transporter distributed in plasma and mitochondrial inner membranes. Mct-1 knockdown also prevented IL-1β-induced expression of phagocyte-type NADPH oxidase (NOX-2), an enzyme specialized for production of ROS, whereas it did not have an effect on inducible NO synthase. Suppression of IL-1β-induced cell death by Nox-2 siRNA indicated that NOX-2 is involved in cell death. Phosphorylation and degradation of inhibitor of κBα (IκBα) from 5 to 20 min after the addition of IL-1β was not affected by Mct-1 siRNA. In addition, IκBα was slightly decreased after 12 h of incubation with IL-1β, and the decrease was prominent after 36 h, whereas activation of p65/RelA was observed from 12 to 48 h after exposure to IL-1β. These changes were not seen in Mct-1-silenced cells. Forced expression of IκBα super repressor as well as treatment with the IκB kinase inhibitor BAY 11-7082 suppressed NOX-2 expression. Furthermore, Mct-1 siRNA lowered the level of ROS generated after 15-h exposure to IL-1β, whereas a ROS scavenger, N-acetylcysteine, suppressed both late phase degradation of IκBα and Nox-2 expression. These results suggest that MCT-1 contributes to NOX-2 expression via late phase activation of NF-κB in a ROS-dependent manner in ATDC5 cells exposed to IL-1β. |
| 巻・号 | 286(17) |
| ページ | 14744-52 |
| 公開日 | 2011-4-29 |
| DOI | 10.1074/jbc.M111.221259 |
| PII | S0021-9258(20)85759-7 |
| PMID | 21372137 |
| PMC | PMC3083201 |
| MeSH | Animals Cell Death Cell Line Chondrocytes / cytology* Interleukin-1beta / pharmacology* Mice Monocarboxylic Acid Transporters / physiology* NADPH Oxidases / biosynthesis* NF-kappa B / metabolism* Nitric Oxide Synthase Type II / biosynthesis Phagocytosis Reactive Oxygen Species Symporters / physiology* |
| IF | 4.238 |
| 引用数 | 17 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |