| 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
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
