| RRC ID |
12431
|
| 著者 |
Akifusa S, Kamio N, Shimazaki Y, Yamaguchi N, Nonaka K, Yamashita Y.
|
| タイトル |
Involvement of the JAK-STAT pathway and SOCS3 in the regulation of adiponectin-generated reactive oxygen species in murine macrophage RAW 264 cells.
|
| ジャーナル |
J Cell Biochem
|
| Abstract |
Adiponectin is a protein hormone produced by differentiating adipocytes and has been proposed to have anti-diabetic and immunosuppressive properties. We previously reported that the globular form of adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO), followed by caspase-dependent apoptotic cell death in RAW 264 cells. Here, we demonstrate that gAd-induced ROS generation and apoptosis were diminished by suppressor of cytokine signaling 3 (SOCS3). The phosphorylation level of signal transducer and activator of transcription (STAT) 3 detected by Western blotting was highest at 20 min in gAd-treated RAW 264 cells. This phosphorylation was inhibited by AG490, a specific inhibitor of janus-activator kinase (JAK). The gAd-induced ROS and NO were reduced by administration of AG490 and Jak-2-specific siRNA in RAW 264 cells. The gAd stimulation transiently induced SOCS3 mRNA expression and protein production. We examined SOCS3-overexpressing RAW 264 cells to investigate the role of the JAK-STAT pathway in gAd-induced ROS and NO generation. SOCS3 overexpression significantly reduced both ROS and NO generation. Additionally, gAd-induced caspase activation and apoptotic cell death were reduced in SOCS3 transfectants compared with vector control transfectants. These results suggest that the JAK-STAT pathway, which can be suppressed by SOCS3 expression, is involved in gAd-induced ROS and NO generation followed by apoptotic cell death.
|
| 巻・号 |
111(3)
|
| ページ |
597-606
|
| 公開日 |
2010-10-15
|
| DOI |
10.1002/jcb.22745
|
| PMID |
20564237
|
| MeSH |
Adiponectin / metabolism*
Animals
Apoptosis
Cell Line
Janus Kinases / metabolism*
Macrophages / metabolism*
Mice
Nitric Oxide / metabolism
Phosphorylation
RNA, Messenger / analysis
Reactive Oxygen Species / metabolism*
STAT Transcription Factors / metabolism
Signal Transduction
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins / biosynthesis
Suppressor of Cytokine Signaling Proteins / genetics
Suppressor of Cytokine Signaling Proteins / metabolism*
|
| IF |
4.237
|
| 引用数 |
12
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
