Laser-Induced Nuclear Damage Signaling and Communication in Astrocyte Networks Through Parp-Dependent Calcium Oscillations
Laser-Induced Nuclear Damage Signaling and Communication in Astrocyte Networks Through Parp-Dependent Calcium Oscillations
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DOI：
10.3389/fphy.2021.598930
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
N. Wakida;Ryan Ha;Edward K. Kim;Xiangduo Kong;K. Yokomori;M. Berns
中科院分区：
文献类型：
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作者：
N. Wakida;Ryan Ha;Edward K. Kim;Xiangduo Kong;K. Yokomori;M. Berns
众所周知，星形胶质细胞会通过钙振荡来响应各种扰动，包括细胞损伤。关于星形胶质细胞检测 DNA/核损伤的能力知之甚少。这项研究着眼于使用近红外钛蓝宝石激光器响应激光诱导的核损伤时钙信号传导的变化。对源自表达 G6Campf 基因编码钙指示剂的基因工程小鼠的原代星形胶质细胞进行成像，以响应激光诱导的损伤。将激光纳米手术与原代星形胶质细胞钙成像相结合，可以对星形胶质细胞网络响应核损伤进行空间和时间观察。核损伤导致核损伤细胞和直接附着在其上的星形胶质细胞的钙峰值频率显着增加。在细胞质受损细胞中没有观察到响应损伤而观察到的钙事件频率的增加以及向邻近细胞的转移。用聚（ADP-核糖）聚合酶抑制剂处理的靶向星形胶质细胞和附着的邻近细胞在激光损伤细胞核后具有显着较低的峰值频率。这些结果表明核损伤后钙峰值频率的增加是聚（ADP-核糖）聚合酶依赖性的。
Astrocytes are known to respond to various perturbations with oscillations of calcium, including to cellular injury. Less is known about astrocytes’ ability to detect DNA/nuclear damage. This study looks at changes in calcium signaling in response to laser-induced nuclear damage using a NIR Ti:Sapphire laser. Primary astrocytes derived from genetically engineered mice expressing G6Campf genetically encoded calcium indicator were imaged in response to laser induced injury. Combining laser nanosurgery with calcium imaging of primary astrocytes allow for spatial and temporal observation of the astrocyte network in response to nuclear damage. Nuclear damage resulted in a significant increase in calcium peak frequency, in nuclear damaged cells and astrocytes directly attached to it. The increase in calcium event frequency observed in response to damage and the transfer to neighboring cells was not observed in cytoplasm damaged cells. Targeted astrocytes and attached neighboring cells treated with Poly (ADP-ribose) polymerase inhibitor have a significantly lower peak frequency following laser damage to the nucleus. These results indicate the increase in calcium peak frequency following nuclear damage is poly (ADP-ribose) polymerase dependent.