Interaction of Human Arylamine N-Acetyltransferase 1 with Different Nanomaterials
Interaction of Human Arylamine N-Acetyltransferase 1 with Different Nanomaterials
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DOI：
10.1124/dmd.113.055988
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发表时间：
2014-03-01
影响因子：
3.9
通讯作者：
Minchin, Rodney F.
中科院分区：
文献类型：
--
作者：
Deng, Zhou J.;Butcher, Neville J.;Minchin, Rodney F.
人类接触到环境中的纳米颗粒以及为生物医学应用开发的纳米材料中的纳米颗粒。然而，许多纳米颗粒的安全性和生物学效应仍有待阐明。在过去的十年里，我们对蛋白质与各种纳米材料的相互作用的了解有所增长。蛋白质电晕不仅可以确定纳米颗粒与细胞的相互作用，还可以确定它们的生物效应和毒性。在这项研究中，我们描述了几种不同类别的纳米颗粒对胞浆蛋白人芳香胺N-乙酰转移酶1(NAT1)的酶活性的影响，NAT1是一种广泛分布于体内的药物代谢酶，也负责已知致癌物的激活和解毒。我们研究了三种金属氧化物(氧化锌、二氧化钛和二氧化硅)，两种合成粘土纳米颗粒(层状双氢氧化物和层状硅酸盐纳米颗粒)，以及一种尺寸和表面特征不同的自组装热响应性聚合物纳米颗粒。我们发现，不同的纳米颗粒引起了非常不同的反应，从抑制到显著增强酶活性。层状硅酸盐不直接使NAT1失活，但发现增强了底物依赖的抑制作用。这些不同的效应证明了纳米颗粒-蛋白质相互作用的多样性，并表明暴露于纳米颗粒的器官，如肺或网状内皮系统，酶活性可能受到损害。
Humans are exposed to nanoparticles in the environment as well as those in nanomaterials developed for biomedical applications. However, the safety and biologic effects of many nanoparticles remain to be elucidated. Over the past decade, our understanding of the interaction of proteins with various nanomaterials has grown. The protein corona can determine not only how nanoparticles interact with cells but also their biologic effects and toxicity. In this study, we describe the effects that several different classes of nanoparticles exert on the enzymatic activity of the cytosolic protein human arylamine N-acetyltransferase 1 (NAT1), a drug-metabolizing enzyme widely distributed in the body that is also responsible for the activation and detoxification of known carcinogens. We investigated three metal oxides (zinc oxide, titanium dioxide, and silicon dioxide), two synthetic clay nanoparticles (layered double hydroxide and layered silicate nanoparticles), and a self-assembling thermo-responsive polymeric nanoparticle that differ in size and surface characteristics. We found that the different nanoparticles induced very different responses, ranging from inhibition to marked enhancement of enzyme activity. The layered silicates did not directly inactivate NAT1, but was found to enhance substrate-dependent inhibition. These differing effects demonstrate the multiplicity of nanoparticle-protein interactions and suggest that enzyme activity may be compromised in organs exposed to nanoparticles, such as the lungs or reticulo-endothelial system.