Uncovering a possible role of reactive oxygen species in magnetogenetics
Uncovering a possible role of reactive oxygen species in magnetogenetics
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DOI：
10.1038/s41598-020-70067-1
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发表时间：
2020-08-04
影响因子：
4.6
通讯作者：
Dordick, Jonathan S.
中科院分区：
文献类型：
--
作者：
Brier, Matthew, I;Mundell, Jordan W.;Dordick, Jonathan S.
最近的报告表明，细胞内（超）顺磁性铁蛋白纳米颗粒可以在磁场中门控TRPV 1（一种非选择性阳离子通道）。在这里，我们报告了不同的场强和频率以及化学抑制剂对通道门控的影响，使用Ca 2+敏感的启动子来表达分泌的胚胎碱性磷酸酶（SEAP）报告。TRPV 1-铁蛋白表达的HEK-293 T细胞在30 ℃暴露于501 kHz和27.1 mT的交变磁场显著增加了SEAP分泌，相对于对照细胞增加了82%，在其他场强和频率下影响较小。在30-32摄氏度之间，通过加入TRPV 1激动剂辣椒素，SEAP的产生强烈增强了3.3倍。这种增强作用被竞争性拮抗剂AMG-21629、NADPH氧化酶组装抑制剂夹竹桃苷和活性氧（ROS）清除剂N-乙酰半胱氨酸消除，表明ROS有助于磁致TRPV 1激活。这些结果为阐明磁遗传学的未知机制提供了理论依据。
Recent reports have shown that intracellular, (super)paramagnetic ferritin nanoparticles can gate TRPV1, a non-selective cation channel, in a magnetic field. Here, we report the effects of differing field strength and frequency as well as chemical inhibitors on channel gating using a Ca2+-sensitive promoter to express a secreted embryonic alkaline phosphatase (SEAP) reporter. Exposure of TRPV1-ferritin-expressing HEK-293T cells at 30 degrees C to an alternating magnetic field of 501 kHz and 27.1 mT significantly increased SEAP secretion by similar to 82% relative to control cells, with lesser effects at other field strengths and frequencies. Between 30-32 degrees C, SEAP production was strongly potentiated 3.3-fold by the addition of the TRPV1 agonist capsaicin. This potentiation was eliminated by the competitive antagonist AMG-21629, the NADPH oxidase assembly inhibitor apocynin, and the reactive oxygen species (ROS) scavenger N-acetylcysteine, suggesting that ROS contributes to magnetogenetic TRPV1 activation. These results provide a rational basis to address the heretofore unknown mechanism of magnetogenetics.