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Co-exposure to silver nanoparticles and cadmium induce metabolic adaptation in HepG2 cells
Nanotoxicology ( IF 5 ) Pub Date : 2018-07-11 , DOI: 10.1080/17435390.2018.1489987
Renata Rank Miranda 1, 2 , Vladimir Gorshkov 2 , Barbara Korzeniowska 2 , Stefan J. Kempf 2 , Francisco Filipak Neto 1 , Frank Kjeldsen 2
Affiliation  

Although multiple studies have reported the toxicological effects and underlying mechanisms of toxicity of silver nanoparticles (AgNP) in a variety of organisms, the interactions of AgNP with environmental contaminants such as cadmium are poorly understood. We used biochemical assays and mass spectrometry-based proteomics to assess the cellular and molecular effects induced by a co-exposure of HepG2 cells to AgNP and cadmium. Cell viability and energy homeostasis were slightly affected after a 4-h exposure to AgNP, cadmium, or a combination of the two; these endpoints were substantially altered after a 24-h co-exposure to AgNP and cadmium, while exposure to one of the two contaminants led only to minor changes. Proteomics analysis followed the same trend: while a 4-h exposure induced minor protein deregulation, a 24-h exposure to a combination of AgNP and cadmium deregulated 43% of the proteome. The toxicity induced by a combined exposure to AgNP and cadmium involved (1) inactivation of Nrf2, resulting in downregulation of antioxidant defense and proteasome-related proteins, (2) metabolic adaptation and ADP/ATP imbalance, and (3) increased protein synthesis possibly to reestablish homeostasis. The adaptation strategy was not sufficient to restore ADP/ATP homeostasis and to avoid cell death.

中文翻译:

共同暴露于银纳米颗粒和镉可诱导HepG2细胞代谢适应

尽管多项研究报告了银纳米颗粒(AgNP)在多种生物中的毒理作用和潜在的毒性机理,但人们对AgNP与环境污染物(例如镉)的相互作用了解甚少。我们使用生化分析和基于质谱的蛋白质组学来评估由HepG2细胞与AgNP和镉共同暴露引起的细胞和分子效应。在暴露于AgNP,镉或两者的组合中4小时后,细胞活力和能量稳态受到了轻微影响。在与AgNP和镉共同暴露24小时后,这些终点发生了显着变化,而暴露于两种污染物之一仅导致较小的变化。蛋白质组学分析遵循相同的趋势:暴露4小时会引起轻微的蛋白质失调,在24小时暴露于AgNP和镉的组合后,蛋白质组的比例降低了43%。联合暴露于AgNP和镉所引起的毒性涉及(1)Nrf2失活,导致抗氧化剂防御和蛋白酶体相关蛋白的下调,(2)代谢适应和ADP / ATP失衡,以及(3)可能增加蛋白合成重新建立体内平衡。适应策略不足以恢复ADP / ATP稳态并避免细胞死亡。
更新日期:2018-08-29
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