Abstract

Titanium dioxide nanomaterials are applied in numerous fields due to their splendid physicochemical characteristics, which in turn poses a potential threat to human health. Recently, numerous in vivo studies have revealed that titanium dioxide nanoparticles (TNPs) can be transported into animal brains after exposure through various routes. Absorbed TNPs can accumulate in the brain and may disturb neuronal cells, leading to brain dysfunction. In vitro studies verified the neurotoxicity of TNPs. The mechanisms underlying the neurotoxicity of TNPs remains unclear. Whether necroptosis is involved in the neurotoxicity of TNPs is unknown. Therefore, we performed an in vitro study and found that TNPs induced inflammatory injury in SH-SY5Y cells in a dose-dependent way, which was mitigated by necrostatin-1 (Nec-1) pretreatment. Since receptor-interacting protein kinase 1 (RIP1) is reported to be the target of Nec-1, we silenced it by siRNA. We exposed mutant and wild-type cells to TNPs and assessed inflammatory injury. Silencing RIP1 expression inhibited inflammatory injury induced by TNPs exposure. Taken together, Nec-1 ameliorates the neurotoxicity of TNPs through RIP1. However, more studies should be performed to comprehensively assess the correlation between the neurotoxicity of TNPs and RIP1.

中文翻译：

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Nec-1通过RIP1减弱二氧化钛纳米材料对Sh-Sy5y细胞的神经毒性。

摘要

二氧化钛纳米材料因其出色的理化特性而在许多领域得到应用，进而对人类健康构成潜在威胁。最近，许多体内研究表明，二氧化钛纳米颗粒（TNP）在通过各种途径暴露后可以转运到动物的大脑中。吸收的TNP可能在大脑中积累，并可能干扰神经元细胞，导致脑功能障碍。体外研究证实了TNP的神经毒性。TNPs的神经毒性的机制尚不清楚。尸体坏死是否参与TNP的神经毒性尚不清楚。因此，我们进行了一项体外研究，发现TNP以剂量依赖的方式诱导SH-SY5Y细胞中的炎症损伤，而坏死抑素-1（Nec-1）预处理可减轻这种损伤。由于据报道受体相互作用蛋白激酶1（RIP1）是Nec-1的靶标，因此我们通过siRNA使其沉默。我们将突变和野生型细胞暴露于TNP并评估炎症损伤。沉默RIP1表达抑制TNPs暴露引起的炎性损伤。总之，Nec-1可通过RIP1改善TNP的神经毒性。但是，应进行更多的研究，以全面评估TNP和RIP1的神经毒性之间的相关性。