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

[神経芽腫細胞でのミトコンドリアおよびメチルグリオキサール関連の代謝促進が50 Hz磁界誘導性の過剰増殖を支える] med./bio.

Improved Mitochondrial and Methylglyoxal-Related Metabolisms Support Hyperproliferation Induced by 50 Hz Magnetic Field in Neuroblastoma Cells.

掲載誌: J Cell Physiol 2016; 231 (9): 2014-2025

この研究は、超低周波磁界(ELF MF: 50Hz、1mT)にばく露したヒト神経芽腫細胞SH-SY5Yで観察された過剰増殖の背景として、メチルグリオキサール(MG)に対する防護の促進、およびエネルギー代謝経路の変更が起きているか否かを調べた。その結果、ELF MFはSH-SY5Y細胞株増殖活性を増加させるだけでなく、MGへの防護を高めることを通して細胞防御メカニズムのトリガーを引くこと、それと併せて、細胞の速い成長を支えるために代謝エネルギー管理の効率を高めることが示された、と報告している。

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研究目的(著者による)

The effects of exposure of human neuroblastoma cells to a 50 Hz magnetic field should be investigated by means of cell proliferation, metabolism and cyto-protective mechanisms to research the role of extremely low frequency magnetic fields in tumor promotion.

詳細情報

In general, tumor cells depend on glycolysis for energy supply and show an increased glycolysis rate compared to normal cells. However, this also increases the production of methylglyoxal, which is a highly cytotoxic and cancer-static glycolytic by-product. Cancer cellular defense mechanisms against methylglyoxal are therefore regarded as a factor associated with tumor promotion. Therefore, in one test approach, 100 µM of methylglyoxal was added to the cells after exposure to the magnetic field and cell growth was investigated after 24 hours.
Several enzymes and biomolecules were investigated:
- Glyoxalases are the main enzymes for the degradation of methylglyoxal.
- Glutathione was investigated as reduced glutathione is an essential cofactor for the degradation of methylglyoxal.
- Argpyrimidine was used as a marker of specific methylglyoxal dependent protein damage.
- GAPDH was measured as it is suggested that it might modify the intracellular methylglyoxal levels.
- The citrate synthase enzyme activity is a marker for mitochondrial activity and PGC-1α is a marker for mitochondrial biogenesis.
- The phosphofructo-kinase is a key enzyme for glycolysis.
- βIII-tubulin was used as a marker for cell differentiation.
All tests were replicated 3-5 times.

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: continuous for 5, 10 or 15 days

ばく露1

主たる特性
周波数 50 Hz
タイプ
  • magnetic field
ばく露時間 continuous for 5, 10 or 15 days
ばく露装置
ばく露の発生源/構造
チャンバの詳細 CO2 incubators
ばく露装置の詳細 solenoids were placed in incubators and produced a highly homogeneous field; temperature in the cell culture was controlled with accuracy better than 0.05°C and no magnetic field-induced heating was observed
Sham exposure A sham exposure was conducted.
Additional information simultaneous exposure and sham exposure in randomly chosen energized and non-energized solenoids
パラメータ
測定量 種別 Method Mass 備考
磁束密度 1 mT - 測定値 - -

Reference articles

  • Sulpizio M et al. (2011): [超低周波磁界(ELF-MF)によって生じる神経芽腫細胞への生物学的影響の根底にある分子的基礎]
  • Di Loreto S et al. (2009): [50Hzの超低周波磁界ばく露はラットの皮質ニューロンに酸化還元及び栄養応答を生じる]
  • Falone S et al. (2007): [50Hz超低周波電磁界は神経芽腫細胞における酸化還元及び分化状態を変化させる]

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)

Exposure to the magnetic field led to a significantly increased cell proliferation after 5-15 days accompanied by a significantly reduced cell differentiation (decrease of βIII-tubulin), indicating a more aggressive tumor growth compared to sham exposure.
After 5 days, the glycolysis and the sensitivity to exogenous methylglyoxal were significantly increased in exposed cells compared to sham exposure. After 15 days, however, an increase in the protective mechanisms against methylglyoxal by means of a significant increase in the quantity and enzyme activity of glyoxalase 2 and the amounts of GAPDH and reduced glutathione was measured in exposed cells compared to sham exposed cells. The resistance of exposed cells to exogenous methylglyoxal was significantly increased after 15 days. In addition, the production of methylglyoxal was reduced by a significant reduction of glycolysis in exposed cells compared to sham-exposed cells, and the mitochondrial activity was significantly increased, presumably to compensate the reduced glycolysis and to support the increased proliferation. The authors pointed out that an increased mitochondrial activity is also associated with a more aggressive tumor growth.
The authors conclude that exposure to a 50 Hz magnetic field could enhance tumor promotion by increasing cell proliferation, enhancing cell-protective mechanisms and establishing a more efficient energy metabolism in human neuroblastoma cells. These changes seemed to be an adaptation process, which was only completed after 15 days of exposure. After 5 days of exposure, a sensitive transition state seemed to be reached.

研究の種別:

研究助成

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