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Involvement of Connexin43 hemichannel in ATP release after $$gamma$$-irradiation

$$gamma$$線照射によるATP放出におけるコネキシン43ヘミチャネルの関与

大島 康宏; 月本 光俊*; 原田 均*; 小島 周二*

Ohshima, Yasuhiro; Tsukimoto, Mitsutoshi*; Harada, Hitoshi*; Kojima, Shuji*

We have recently reported that $$gamma$$-irradiation induces ATP release from B16 melanoma cells, which is dependent on P2X$$_{7}$$ receptor. However, the mechanism of ATP release caused by irradiation remains unclear. We here show the involvement of Cx43 in P2X$$_{7}$$ receptor-dependent ATP release after 0.5 Gy $$gamma$$-irradiation. Inhibitors of gap junction hemichannels and an inhibitory peptide for Cx43 (gap26), but not an inhibitory peptide for pannexin1 (Panx1), significantly blocked $$gamma$$-irradiation-induced ATP release from B16 melanoma cells. We confirmed high expression of Cx43 mRNA in B16 melanoma cells. These results suggest involvement of Cx43 in the radiation-induced ATP release. We found that tyrosine phosphorylation after 0.5 Gy $$gamma$$-irradiation was significantly blocked by P2X$$_{7}$$ receptor antagonist, but not gap26, suggesting that tyrosine phosphorylation is a downstream event from P2X$$_{7}$$ receptor. Since tyrosine kinase inhibitor significantly suppressed radiation-induced ATP release, tyrosine phosphorylation appears to play an important role in the Cx43-mediated ATP release downstream of P2X$$_{7}$$ receptor. In conclusion, the Cx43 hemichannel, which lies downstream of P2X$$_{7}$$ receptor, is involved in ATP release in response to radiation.

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パーセンタイル:81.85

分野:Biology

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