この研究は、マウスのN9ミクログリア細胞活性化に対する2.45 GHz 電磁界ばく露の影響を調べた。シグナル伝達兼転写活性化因子 （STAT3）の蛋白質発現、ヤヌスチロシンキナーゼ1及び2（JAK1及びJAK2）、リン酸化STAT3、STAT3のDNA結合活性はウエスタンブロット分析と電気泳動移動度シフトアッセイ（EMSA）によって測定した。一酸化窒素（NO）誘導体である亜硝酸塩のレベルはグリース反応によって測定した。腫瘍壊死因子α（TNF-α）と誘導型一酸化窒素合成酵素（iNOS）のmRNA発現はRT-OCRで検出した。その結果、EMFばく露がミクログリア細胞の活性化を開始させ、STAT3シグナル伝達がこの活性化に関与することを示す所見が見られたことを報告している。
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To study the activation of microglia and involvement of signal transducer and activator of transcription 3 (STAT3; mediates signal transduction from the extracellular environment to the nucleus) in microglia activation after 2.45 GHz electromagnetic fields exposure.
Microglia is considered as a specialised macrophages residing form in the central nervous system. In response to a variety of insults, microglia adopts an activated phenotype. Microglia activation plays a pivotal role in the initiation and progression of several neurodegenerative diseases.
Some cell samples were pretreated with the JAK inhibitor pyridone 6 (P6) to study whether P6 could affect the STAT3 activation (to further demonstrate JAK2-STAT3 signal transduction (JAK is a STAT3 activator and is able to phosphorylate STAT3)). Cells were investigated 1 h, 6 h, and 12 h after exposure.
| 周波数 | 2.45 GHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 20 min |
| Modulation type | pulsed |
|---|---|
| Pulse width | 2 µs |
| Packets per second | 500 |
The data showed a significant increase of STAT3 DNA-binding ability after exposure. Consistent with this, the electromagnetic field exposure rapidly induced phosphorylation of STAT3 and activated JAK1 and JAK2. Additionally, electromagnetic field exposure increased transcription levels of the inflammation-associated genes (iNOS and TNF-alpha), which are reported to contain STAT-binding elements in their promoter region.
P6 reduced induction of iNOS and TNF-alpha, DNA binding activity, and activation of STAT3 in exposure-stimulated microglia cells. These findings indicate that the electromagnetic field exposure induces phosphorylation and activation of STAT3 through phosphorylation and activation of JAK.
The authors conclude that the data provide evidence that electromagnetic field exposure can initiate the activation of microglia cells and that STAT3 signal transduction is involved in electromagnetic field-induced microglial activation.
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