Online ISSN: 1884-4111 Print ISSN: 0033-8303
Radioisotopes 65(3): 137-143 (2016)


X線照射はPC12細胞における神経成長因子誘導の神経軸索伸長を促進するXray Irradiation Promotes Nerve Growth Factor-induced Neurite Extension in PC12 Cells

1横浜薬科大学放射線科学研究室Department of Radiation Science, Yokohama University of Pharmacy ◇ 245–0066 神奈川県横浜市戸塚区俣野町601 ◇ 601 Matano-cho, Totsuka-ku, Yokohama-shi, Kanagawa Pref. 245–0066, Japan

2京都大学放射線生物研究センターRadiation Biology Center, Kyoto University ◇ 606–8501 京都府京都市左京区吉田近衛町 ◇ Yoshidakonoe-cho, Sakyo-ku, Kyoto-shi, Kyoto 606–8501, Japan

3横浜薬科大学総合健康メディカルセンターGeneral Health Medical Center, Yokohama University of Pharmacy ◇ 245–0066 神奈川県横浜市戸塚区俣野町601 ◇ 601 Matano-cho, Totsuka-ku, Yokohama-shi, Kanagawa Pref. 245–0066, Japan

4帝京大学医療技術学部診療放射線学科Clinical Radiology, Faculty of Medical Technology, Teikyo University ◇ 173–8605 東京都板橋区加賀2–11–1 ◇ 2–11–1 Kaga, Itabashi-ku, Tokyo 173–8605, Japan

受付日:2015年10月30日Received: October 30, 2015
受理日:2016年1月8日Accepted: January 8, 2016
発行日:2016年3月15日Published: March 15, 2016

X線500 mGyの照射により,神経成長因子(NGF)によるPC12細胞の神経軸索伸長が促進された。このとき,NGFの主要な細胞内シグナル分子ERKのリン酸化は増加していたが,NGF受容体自身のリン酸化は亢進していなかった。興味深いことに,増殖シグナルを活性化する上皮成長因子(EGF)の受容体のリン酸化が照射によって亢進されており,これを阻害剤にて抑制したところ,照射によるNGF誘導神経軸索伸長の促進は抑えられた。以上の結果から,X線照射によるEGF受容体のリン酸化の亢進がNGFシグナルとのクロストーク経路を介して,NGF誘導の神経軸索伸長を促進していることが示唆された。

Nerve growth factor (NGF) induces neurite extension in PC12 cells, a well-known model of neuronal differentiation. Previous reports have shown that irradiation activates the extracellular signal-regulated kinase 1/2 (ERK), which is a mainstream pathway for NGF signaling. This suggests that the neurite extension may possibly be enhanced by Xray irradiation. Therefore, we observed NGF-induced neurite extension with Xray irradiation in PC12 cells. At the start of the NGF treatment, Xray irradiation was performed simultaneously for the first 5 min. After 5 days, the irradiation at 500 mGy promoted NGF-induced neurite extension, and increased phosphorylation of ERK, but not of the NGF receptor. The phosphorylation of epidermal growth factor (EGF) receptor, a stimulatory growth signal in PC12 cells, was also enhanced by irradiation. Interestingly, AG1478, an inhibitor of EGF receptor tyrosine kinase, inhibited the irradiation-induced promotion of neurite extension. These results suggest that irradiation activate EGF receptor tyrosine kinase and promote NGF-induced neurite extension via the cross talk between NGF and EGF signaling.

Key words: neural differetiation; nerve growth factor; neurite extension; Xray irradiation; PC12 cells

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