鞘氨醇-1-磷酸通过TRPC6通道引发SH-SY5Y细胞和海马神经元的钙信号  

Sphingosine-1-phosphate induces Ca2+mobilization via TRPC6 channels in SH-SY5Y cells and hippocampal neurons

作　　者：吴浩天 林冰倩 李灿军 曾文萍 曲莉丽 仓春蕾 Haotian Wu;Bingqian Lin;Canjun Li;Wenping Zeng;Lili Qu;Chunlei Cang(School of Basic Medical Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230026,China;Institute on Aging and Brain Disorders,the First Affiliated Hospital of USTC,University of Science and Technology of China,Hefei 230036,China)

机构地区：[1]中国科学技术大学生命科学与医学部基础医学院,安徽合肥230026 [2]中国科学技术大学附属第一医院脑衰老与脑疾病研究中心,安徽合肥230036

出　　处：《中国科学技术大学学报》2022年第9期11-20,I0002,共11页JUSTC

基　　金：the National Natural Science Foundation of China(31770896)。

摘　　要：鞘氨醇-1-磷酸(sphingosine-1-phosphate,S1P)是一种广泛表达的具有生物活性的鞘脂,在细胞分化、迁移、增殖、代谢和凋亡中发挥重要作用。S1P可以激活多种信号通路,其中的一些能够引发细胞质中的Ca信号,但很少有研究关注S1P引发神经元Ca信号的机制。在本研究中,我们发现S1P可以在SH-SY5Y细胞和海马神经元中引发Ca信号。去除细胞外的钙离子在很大程度上消除了S1P诱导的细胞内Ca增加,表明细胞外Ca的内流是这一过程的主要贡献者。此外,我们发现S1P诱导的Ca信号不依赖于G蛋白偶联的S1P受体或者表皮生长因子的反式激活。TRPC6的抑制剂SAR7334抑制了S1P诱导的钙信号,表明TRPC6通道充当S1P的下游效应器。使用膜片钳记录,我们发现S1P可以激活TRPC6电流。两种Src酪氨酸激酶抑制剂Src-I1和PP2可以显著抑制S1P对TRPC6的激活。总之,我们的数据表明S1P以一种Src依赖性方式激活TRPC6通道,进而诱导SH-SY5Y细胞和海马神经元中的Ca信号。Sphingosine-1-phosphate(S1P)is a widely expressed biologically active sphingolipid that plays an important role in cell differentiation,migration,proliferation,metabolism and apoptosis.S1P activates various signaling pathways,some of which evoke Casignals in the cytosol.Few studies have focused on the mechanism by which S1P evokes Casignals in neurons.Here,we show that S1P evokes global Casignals in SH-SY5Y cells and hippocampal neurons.Removal of extracellular calcium largely abolished the S1P-induced increase in intracellular Ca,suggesting that the influx of extracellular Cais the major contributor to this process.Moreover,we found that S1P-induced Camobilization is independent of G protein-coupled S1P receptors.The TRPC6 inhibitor SAR7334 suppressed S1P-induced calcium signals,indicating that the TRPC6 channel acts as the downstream effector of S1P.Using patch-clamp recording,we showed that S1P activates TRPC6 currents.Two Src tyrosine kinase inhibitors,Src-I1 and PP2,dramatically inhibited the activation of TRPC6 by S1P.Taken together,our data suggest that S1P activates TRPC6 channels in a Src-dependent way to induce Camobilization in SH-SY5Y cells and hippocampal neurons.

关 键 词：鞘氨醇-1-磷酸 钙离子 TRPC6通道 SRC激酶 SH-SY5Y 神经元 

分 类 号：Q189[生物学—神经生物学]