研究のタイプ: 医学/生物学の研究 (experimental study)

[超低周波電磁界へのばく露はアラキドン酸/ロイコトリエンE4シグナル伝達経路を介してT型カルシウムチャネルを阻害する] med./bio.

Exposure to extremely low-frequency electromagnetic fields inhibits T-type calcium channels via AA/LTE signaling pathway

掲載誌: Cell Calcium 2014; 55 (1): 48-58

この研究は、細胞株HEK293に導入されたヒトT型カルシウムイオンチャネル低電圧依存性)に対する低周波電磁界(ELF-EMF;50 Hz、0.2 mT)の影響を調べた。その結果、ELF-EMFは、全てのT型チャネル(Cav3.1、Cav3.2、Cav3.3)を阻害した;Cav3.2のタンパク発現、定常状態での活性化・不活化の動力学のどちらもELF-EMFによる変化を起こさなかった;HEK293細胞のアラキドン酸(AA)およびロイコトリエンE4(LTE4)レベルは両方ともELF-EMFによって上昇した;AAおよびLTE4それぞれの阻害剤を添加すると、Cav3.2に対するELF-EMFの阻害作用は消えた、などを報告している。

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研究目的(著者による)

To investigate the effects of extremely low frequency magnetic fields on human T-type calcium channels transfected in embryonic kidney cells and on native T-type calcium channels in cultured mouse cortical neurons.

詳細情報

T-type calcium channels are low-voltage activated calcium channels. They play key roles in various physiological and pathological functions.
The T-type calcium channels Cav3.1, Cav3.2 and Cav3.3 were transfected in human embryonic kidney cells.
The primary cultured cortical neurons were used to test whether magnetic field exposure inhibits native T-type channel currents via a leukotriene E4 pathway.
Leukotriene E4 is produced by the oxidation of arachidonic acid and involved in inflammation processes.
Experiments were partially performed with the inhibitors CAY10502 (inhibits the release of arachidonic acid), BAYµ9773 (leukotriene receptor antagonist) or bestatin (blocks the conversion from leukotrien D4 to leukotrien E4).

影響評価項目

ばく露

ばく露 パラメータ
ばく露1: 50 Hz
ばく露時間: continuously for up to 3 hours (0.5 h, 1 h, 2 h, 3 h)

ばく露1

主たる特性
周波数 50 Hz
タイプ
  • magnetic field
波形
  • unspecified
ばく露時間 continuously for up to 3 hours (0.5 h, 1 h, 2 h, 3 h)
ばく露装置
ばく露の発生源/構造
ばく露装置の詳細 magnetic field was produced by a pair of Helmholtz coils, powered by an AC generator system; exposure did not change the temperature of the CO2 incubator (37 °C)
Sham exposure A sham exposure was conducted.
Additional information sham exosed control group was placed in the same incubator but without magnetic field
パラメータ
測定量 種別 Method Mass 備考
磁束密度 200 µT unspecified 測定値 - -

Reference articles

  • He YL et al. (2013): [超低周波電磁界へのばく露はAA/PGE2経路およびEP受容体介在性cAMP/PKA経路の生成レベル上昇によりラット小脳顆粒細胞のナトリウムイオン電流を変化させる]

ばく露を受けた生物:

方法 影響評価項目/測定パラメータ/方法

研究対象とした生物試料:
調査の時期:
  • ばく露後

研究の主なアウトカム(著者による)

In exposed cell cultures of embryonic kidney cells, the cell currents were significantly decreased after 0.5 and 1 hour exposure compared to the control group. That means that the T-type channels (Cav3.1, Cav3.2 and Cav3.3) were inhibited. The inhibitor CAY10502 and bestatin abrogated the exposure-related inhibitory effect. To further verify the results, leukotriene E4 was added to the culture medium, which mimicked the exposure-related inhibition of calcium channels. However, neither the expression of the T-type channel Cav3.2 nor the steady-state activation and inactivation kinetics were changed by exposure. Arachidonic acid and leukotriene E4 were significantly increased after 0.5 and 1 hour exposure in comparison to the control group.
In primary cultured mouse cortical neurons, the exposure significantly inhibited the T-type channel currents when compared to the control group. Experiments with the inhibitor bestatin and addition of leukotriene E4 indicated that the inhibition is mediated via a leukotriene E4 pathway.
The authors conclude that extremely low frequency magnetic fields inhibit T-type calcium channels in transfected embryonic kidney cells and primary cultured cortical neurons through an arachidonic acid and leukotriene E4 dependent pathway.

研究の種別:

研究助成

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