Gilardino Alessandra, Catalano Federico, Ruffinatti Federico Alessandro, Alberto Gabriele, Nilius Bernd, Antoniotti Susanna, Martra Gianmario, Lovisolo Davide
Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy; NIS Centre, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy.
Department of Chemistry, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy; NIS Centre, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy.
Int J Biochem Cell Biol. 2015 Sep;66:101-11. doi: 10.1016/j.biocel.2015.07.012. Epub 2015 Jul 26.
SiO2 nanoparticles (NPs), in addition to their widespread utilization in consumer goods, are also being engineered for clinical use. They are considered to exert low toxicity both in vivo and in vitro, but the mechanisms involved in the cellular responses activated by these nanoobjects, even at non-toxic doses, have not been characterized in detail. This is of particular relevance for their interaction with the nervous system: silica NPs are good candidates for nanoneuromedicine applications. Here, by using two neuronal cell lines (GT1-7 and GN11 cells), derived from gonadotropin hormone releasing hormone (GnRH) neurons, we describe the mechanisms involved in the perturbation of calcium signaling, a key controller of neuronal function. At the non-toxic dose of 20μgmL(-1), 50nm SiO2 NPs induce long lasting but reversible calcium signals, that in most cases show a complex oscillatory behavior. Using fluorescent NPs, we show that these signals do not depend on NPs internalization, are totally ascribable to calcium influx and are dependent in a complex way from size and surface charge. We provide evidence of the involvement of voltage-dependent and transient receptor potential-vanilloid 4 (TRPV4) channels.
二氧化硅纳米颗粒（NPs）除了在消费品中广泛应用外，也正被设计用于临床。它们被认为在体内和体外都具有低毒性，但是这些纳米物体激活的细胞反应所涉及的机制，即使在无毒剂量下，也尚未得到详细表征。这对于它们与神经系统的相互作用尤为重要：二氧化硅纳米颗粒是纳米神经医学应用的良好候选者。在这里，我们使用两种源自促性腺激素释放激素（GnRH）神经元的神经元细胞系（GT1-7和GN11细胞），描述了钙信号传导紊乱所涉及的机制，钙信号传导是神经元功能的关键控制器。在20μgmL(-1)的无毒剂量下，50nm的二氧化硅纳米颗粒会诱导持久但可逆的钙信号，在大多数情况下，这些信号表现出复杂的振荡行为。使用荧光纳米颗粒，我们表明这些信号不依赖于纳米颗粒的内化，完全归因于钙内流，并且以复杂的方式依赖于尺寸和表面电荷。我们提供了电压依赖性和瞬时受体电位香草酸亚型4（TRPV4）通道参与的证据。
