携帯電話によって発生する非熱的マイクロ波電磁界へのばく露は、多くのタンパク質の発現に影響を及ぼす。転写とタンパク質安定性への影響は、中心的な信号伝達経路であり、基本的に細胞刺激の全過程を支配するMARK(マイトジェン活性化タンパク質キナーゼ)カスケードによって仲介される可能性がある。確かに、細胞が携帯電話の放射に長期間ばく露されることによって、ERK(細胞外シグナル調節キナーゼ)MAPKsとともにp38の活性化が生じる。本研究で、我々はMAPKカスケードに対する放射の急性的影響を調査し、ストレス関連のMARKsではなくERKsが様々な周波数と強度に反応して、素早く活性化することを見出した。信号伝達阻害剤を使って、この活性化に関係するメカニズムを正確に描きだした。第一段階は、原形質膜上で迅速にROS（活性酵素種）を発生させるNADH酸化酵素によって仲介されることが見出された。次に、これらのROSは直接MMPs(マトリクス・メタロプロテイナーゼ)を刺激し、それによってMMPsは裂け、Hb－EGF[ヘパリン結合EGF(上皮細胞増殖因子)]が放出される。この分泌された因子はEGF受容体を活性化させ、次の段階でERKカスケードを活性化させる。このように、本研究は、携帯電話からの電磁波放射がERKカスケードの活性化を引き起こし、それによって転写と他の細胞作用を引き起こすという分子的メカニズムの詳細を初めて検証した。
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To study the effect of electromagnetic fields at mobile phone frequency on the MAPK (mitogen-activated protein kinase) cascades.
MAPK cascades (ERK1/2, JNK1-3, p38MAPK, BMK1) are a group of signal transduction pathways, which mediate the effects of various extracellular stimuli to regulate processes including proliferation, differentiation, metabolism and stress response.
Cells as well as isolated membranes of HeLa cells were used. Different inhibitors (reactive oxygen species inhibitor/scavenger, EGF receptor inhibitor, NADH oxidase inhibitor etc.) were used to identify mediators of irradiation-induced ERKs phosphorylation (signals are transmitted via phosphorylations of protein kinases and of regulatory proteins, for example).
| ばく露 | パラメータ |
|---|---|
|
ばく露1:
875 MHz
ばく露時間:
continuous for 5, 10, (15,) 20, and 30 min
|
|
|
ばく露2:
875 MHz
ばく露時間:
continuous for 10 min
|
|
|
ばく露3:
875 MHz
ばく露時間:
continuous for 5, 10, 20, and 30 min
|
|
|
ばく露4:
800–950 MHz
ばく露時間:
continuous for 5, 10, 20, and 30 min
|
|
|
ばく露5:
875 MHz
ばく露時間:
continuous for 10 min
|
|
|
ばく露6:
875 MHz
ばく露時間:
continuous for 2 or 12 min
|
|
|
ばく露7:
875 MHz
ばく露時間:
continuous for 10 min
|
|
|
ばく露8:
875 MHz
ばく露時間:
continuous for 2, 5, 12, and 20 min
|
|
|
ばく露9:
875 MHz
ばく露時間:
continuous for 10 or 5 min
|
|
|
ばく露10:
875 MHz
ばく露時間:
continuous for 5, 10, and 15 min
|
|
|
ばく露11:
875 MHz
ばく露時間:
continuous for 15 and 30 min
|
|
|
ばく露12:
875 MHz
ばく露時間:
continuous for 5 and 10 min
|
|
|
ばく露13:
875 MHz
ばく露時間:
continuous for 10, 20, and 30 min
|
|
| 周波数 | 875 MHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 5, 10, (15,) 20, and 30 min |
| ばく露の発生源／構造 |
|
|---|---|
| Distance between exposed object and exposure source | 10 cm |
| チャンバの詳細 | The walls of the incubator with 5% CO2 humidified air at 37°C were covered with RF-absorbing material. |
| ばく露装置の詳細 | Cells were irradiated in 6-cm dishes inside the incubator. |
| Sham exposure | A sham exposure was conducted. |
| 周波数 | 875 MHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 10 min |
| 測定量 | 値 | 種別 | Method | Mass | 備考 |
|---|---|---|---|---|---|
| 電力密度 | 0.21 mW/cm² | - | 測定値 | - | - |
| 周波数 | 875 MHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 2 or 12 min |
| ばく露の発生源／構造 |
|
|---|---|
| Sham exposure | A sham exposure was conducted. |
| Additional information | Some cells were left in the incubator for another 5 or 10 min after their 2-min exposure. |
| 測定量 | 値 | 種別 | Method | Mass | 備考 |
|---|---|---|---|---|---|
| 電力密度 | 0.17 mW/cm² | - | 測定値 | - | - |
| 周波数 | 875 MHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 2, 5, 12, and 20 min |
| ばく露の発生源／構造 |
|
|---|---|
| Sham exposure | A sham exposure was conducted. |
| Additional information | Some cells were left in the incubator for another 5 or 10 min after their 2-min exposure. |
| 測定量 | 値 | 種別 | Method | Mass | 備考 |
|---|---|---|---|---|---|
| 電力密度 | 0.31 mW/cm² | - | 測定値 | - | - |
| 周波数 | 875 MHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 10 or 5 min |
| 周波数 | 875 MHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 5, 10, and 15 min |
| ばく露の発生源／構造 |
|
|---|---|
| Sham exposure | A sham exposure was conducted. |
| 測定量 | 値 | 種別 | Method | Mass | 備考 |
|---|---|---|---|---|---|
| 電力密度 | 0.344 mW/cm² | - | 測定値 | - | - |
| 周波数 | 875 MHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 15 and 30 min |
| ばく露の発生源／構造 |
|
|---|---|
| ばく露装置の詳細 | Membranes suspended in PBS (100 µl) were irradiated in a thin tube inside the incubator. |
| Sham exposure | A sham exposure was conducted. |
| Additional information | After incubation for 15 min with various inhibitors, the membranes or controls were either irradiated or left untreated. |
| 測定量 | 値 | 種別 | Method | Mass | 備考 |
|---|---|---|---|---|---|
| 電力密度 | 0.3 mW/cm² | - | 測定値 | - | - |
| 周波数 | 875 MHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 5 and 10 min |
| ばく露の発生源／構造 |
|
|---|---|
| ばく露装置の詳細 | Membranes suspended in PBS (100 µl) were irradiated in a thin tube inside the incubator. |
| Sham exposure | A sham exposure was conducted. |
| 測定量 | 値 | 種別 | Method | Mass | 備考 |
|---|---|---|---|---|---|
| 電力密度 | 0.24 mW/cm² | - | 測定値 | - | - |
| 周波数 | 875 MHz |
|---|---|
| タイプ |
|
| ばく露時間 | continuous for 10, 20, and 30 min |
| 測定量 | 値 | 種別 | Method | Mass | 備考 |
|---|---|---|---|---|---|
| 電力密度 | 0.2 mW/cm² | - | 測定値 | - | - |
This study delineate a detailed molecular mechanism by which electromagnetic fields at mobile phone frequency induces short-term MAPK activation and thereby transcription and other cellular processes.
The data show that ERKs, but not JNKs or p38MAPKs, are rapidly activated in response to mobile phone exposure at various frequencies and intensities. The first step is mediated in the plasma membrane by NADH oxidase, which rapidly generates reactive oxygen species. The generated reactive oxygen species then directly activate matrix metalloproteinases to release heparin-binding (Hb)-EGF, which further activate the ERK cascade.
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