Medical School, Southeast University, Nanjing, 210009, China.
College of Life Sciences, Nanjing Agricultural University, Nanjing, 210095, China.
Sci Rep. 2019 Apr 15;9(1):6026. doi: 10.1038/s41598-019-42603-1.
Exposure to graphene oxide (GO) induced some dysregulated microRNAs (miRNAs), such as the increase in mir-247, in nematode Caenorhabditis elegans. We here further identified goa-1 encoding a Gαo and pkc-1 encoding a serine/threonine protein kinase as the targets of neuronal mir-247 in the regulation of GO toxicity. GO exposure increased the expressions of both GOA-1 and PKC-1. Mutation of goa-1 or pkc-1 induced a susceptibility to GO toxicity, and suppressed the resistance of mir-247 mutant to GO toxicity. GOA-1 and PKC-1 could also act in the neurons to regulate the GO toxicity, and neuronal overexpression of mir-247 could not affect the resistance of nematodes overexpressing neuronal goa-1 or pkc-1 lacking 3'-UTR to GO toxicity. In the neurons, GOA-1 acted upstream of diacylglycerol kinase/DGK-1 and PKC-1 to regulate the GO toxicity. Moreover, DGK-1 and GOA-1 functioned synergistically in the regulation of GO toxicity. Our results highlight the crucial role of neuronal Gαo signaling in response to GO in nematodes.
氧化石墨烯（GO）暴露会引起一些失调的 microRNAs（miRNAs），如线虫秀丽隐杆线虫中 mir-247 的增加。我们进一步确定编码 Gαo 的 goa-1 和编码丝氨酸/苏氨酸蛋白激酶的 pkc-1 是神经元 mir-247 调节 GO 毒性的靶标。GO 暴露增加了 GOA-1 和 PKC-1 的表达。goa-1 或 pkc-1 的突变会导致对 GO 毒性的易感性，并抑制 mir-247 突变体对 GO 毒性的抵抗力。GOA-1 和 PKC-1 也可以在神经元中发挥作用，调节 GO 毒性，神经元过表达 mir-247 不会影响神经元过表达缺乏 3'-UTR 的神经元 goa-1 或 pkc-1 的线虫对 GO 毒性的抗性。在神经元中，GOA-1 在前 DGK-1 和 PKC-1 上游发挥作用，调节 GO 毒性。此外，DGK-1 和 GOA-1 在调节 GO 毒性方面协同作用。我们的研究结果强调了神经元 Gαo 信号在线虫对 GO 反应中的关键作用。
