Purinergic Signaling Is a Novel Mechanism of the Cellular Response to Ionizing Radiation.
Purinergic Signaling Is a Novel Mechanism of the Cellular Response to Ionizing Radiation.
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嘌呤能信号传导是细胞对电离辐射反应的一种新机制。
DOI：
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发表时间：
2015
影响因子：
2
通讯作者：
Mitsutoshi Tsukimoto
中科院分区：
文献类型：
--
作者：
Mitsutoshi Tsukimoto
最近的研究表明，辐射效应不仅在受辐射的细胞中观察到，而且在邻近的未受辐射的细胞中也观察到（旁观者效应），尽管其机制尚未完全揭示。这种旁观者效应可能是由通过间隙连接的细胞间通讯或受辐射细胞释放的信使（例如活性氧、一氧化氮或细胞因子）引起的。然而，旁观者效应也可能存在未知的机制。另一方面，已知从细胞释放的细胞外ATP、ADP、尿苷5'-三磷酸（UTP）和尿苷5'-二磷酸（UDP）通过激活嘌呤能P2X和P2Y受体（嘌呤能信号传导）而充当细胞间信号传导分子。最近，我提出这些细胞外核苷酸可能是辐射诱导的旁观者效应的新介质，因为我们最近的研究表明嘌呤能信号传导参与了重要的细胞对辐射的反应。我们的数据表明，电离辐射会激活瞬态受体电位褪黑素2型（TRPM2）通道，然后通过P2X7受体激活介导的阴离子通道或连接蛋白43半通道从细胞中释放ATP。释放的核苷酸激活 P2Y6 和 P2Y12 受体，这些受体参与辐射后的 DNA 损伤反应。 P2Y6 受体的激活还参与辐射诱导的上皮生长因子受体-细胞外信号调节蛋白激酶 (EGFR-ERK)1/2 通路的激活以及随后的 EGFR 核转位，从而在 DNA 修复中发挥作用。此外，辐射后抗氧化剂的诱导也是由 P2Y 受体的激活介导的。总之，嘌呤能信号在电离辐射的保护性细胞反应中发挥重要作用。
Recent studies suggest the effect of radiation is observed not only in irradiated cells but also in adjacent non-irradiated cells (bystander effect), although the mechanism has not yet been fully revealed. This bystander effect may be caused by intercellular communication via a gap junction or by messengers released from irradiated cells, such as reactive oxygen species, nitric oxide, or cytokines. However, an unknown mechanism is also possible in the bystander effect. On the other hand, it is known that extracellular ATP, ADP, uridine 5'-triphosphate (UTP), and uridine 5'-diphosphate (UDP), which are released from cells, act as intercellular signaling molecules by activating purinergic P2X and P2Y receptors (purinergic signaling). Recently, I have suggested these extracellular nucleotides may be novel mediators of a radiation-induced bystander effect, because our recent studies indicated that purinergic signaling is involved in important cellular responses to radiation. Our data indicate that ionizing irradiation causes activation of the transient receptor potential melastatin type 2 (TRPM2) channel, and then ATP is released from cells through the anion channel or connexin43 hemichannel mediated by the activation of a P2X7 receptor. The released nucleotides activate P2Y6 and P2Y12 receptors, which are involved in the DNA damage response after irradiation. Activation of the P2Y6 receptor is also involved in radiation-induced activation of the epithelial growth factor receptor-extracellular signal regulated protein kinase (EGFR-ERK)1/2 pathway and subsequent nuclear translocation of EGFR, which plays a role in DNA repair. Further, the induction of an antioxidant after irradiation is also mediated by the activation of the P2Y receptor. In conclusion, purinergic signaling could play an important role in the protective cellular response to ionizing irradiation.
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影响因子：
11.2
作者：
E. Azzam;S. M. de Toledo;D. Spitz;J. Little
通讯作者：
E. Azzam;S. M. de Toledo;D. Spitz;J. Little
影响因子：
4.7
作者：
Li, Shengqing;Bode, Ann M.;Dong, Zigang
通讯作者：
Dong, Zigang
DOI：
10.1073/pnas.030420797
发表时间：
2000-02-29
影响因子：
11.1
作者：
Zhou, HN;Randers-Pehrson, G;Hei, TK
通讯作者：
Hei, TK
DOI：
--
发表时间：
2001
影响因子：
11.1
作者：
H. Zhou;M. Suzuki;G. Randers-Pehrson;D. Vannais;G. Chen;J. Trosko;C. Waldren;T. Hei
通讯作者：
H. Zhou;M. Suzuki;G. Randers-Pehrson;D. Vannais;G. Chen;J. Trosko;C. Waldren;T. Hei
影响因子：
5.5
作者：
Iglesias, R.;Locovei, S.;Scemes, E.
通讯作者：
Scemes, E.