Graphene oxide disrupted mitochondrial homeostasis through inducing intracellular redox deviation and autophagy-lysosomal network dysfunction in SH-SY5Y cells
Graphene oxide disrupted mitochondrial homeostasis through inducing intracellular redox deviation and autophagy-lysosomal network dysfunction in SH-SY5Y cells
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氧化石墨烯通过诱导 SH-SY5Y 细胞内氧化还原偏差和自噬-溶酶体网络功能障碍破坏线粒体稳态
DOI：
10.1016/j.jhazmat.2021.126158
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发表时间：
2021-05-27
影响因子：
13.6
通讯作者：
Shao Longquan
中科院分区：
文献类型：
--
作者：
Feng Xiaoli;Zhang Yaqing;Shao Longquan
氧化石墨烯（GO）纳米材料在神经科学中的药物递送和电极材料方面具有显著的优势，然而，它们对中枢神经系统（CNS）的暴露风险和毒性问题也增加了。目前关于GO诱导的神经毒性的研究仍然不明确，更不用说复杂的GO化学如何影响其与神经细胞的生物学行为的机制了。在这项研究中，我们详细描述了市售GO的特征，并使用培养的SH-SY 5 Y细胞研究了其生物学不良反应。我们发现，在介质中的超声处理改变了氧化状态和表面活性的平面表面上的GO由于其水化活性，引起脂质过氧化和细胞膜损伤。随后，在GO内化后观察到ROS破坏线粒体稳态，这是由NOX 2信号传导的激活引起的。自噬-溶酶体网络作为一种防御反应启动，以清除氧化损伤的线粒体和外来纳米材料，由于溶酶体降解能力降低，这是无效的。这些连续的细胞反应加剧了线粒体应激，导致凋亡性细胞死亡。这些数据突出了GO的结构相关活性对其生物学特性的重要性，并提供了对GO衍生的细胞氧化还原信号传导如何诱导调节细胞功能和存活的cadion相关级联的深入理解。
Graphene oxide (GO) nanomaterials have significant advantages for drug delivery and electrode materials in neural science, however, their exposure risks to the central nervous system (CNS) and toxicity concerns are also increased. The current studies of GO-induced neurotoxicity remain still ambiguous, let alone the mechanism of how complicated GO chemistry affects its biological behavior with neural cells. In this study, we characterized the commercially available GO in detail and investigated its biological adverse effects using cultured SH-SY5Y cells. We found that ultrasonic processing in medium changed the oxidation status and surface reactivity on the planar surface of GO due to its hydration activity, causing lipid peroxidation and cell membrane damage. Subsequently, ROS-disrupted mitochondrial homeostasis, resulting from the activation of NOX2 signaling, was observed following GO internalization. The autophagy-lysosomal network was initiated as a defensive reaction to obliterate oxidative damaged mitochondria and foreign nanomaterials, which was ineffective due to reduced lysosomal degradation capacity. These sequential cellular responses exacerbated mitochondrial stress, leading to apoptotic cell death. These data highlight the importance of the structure-related activity of GO on its biological properties and provide an in-depth understanding of how GO-derived cellular redox signaling induces mitochondrion-related cascades that modulate cell functionality and survival.