Feng Po-Hao, Huang Ya-Li, Chuang Kai-Jen, Chen Kuan-Yuan, Lee Kang-Yun, Ho Shu-Chuan, Bien Mauo-Ying, Yang You-Lan, Chuang Hsiao-Chi
Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
Chem Biol Interact. 2015 Jul 5;236:82-9. doi: 10.1016/j.cbi.2015.05.003. Epub 2015 May 13.
Protein oxidation is considered to be one of the main causes of cell death, and methionine is one of the primary targets of reactive oxygen species (ROS). However, the mechanisms by which nickel nanoparticles (NiNPs) cause oxidative damage to proteins remain unclear.
The objective of this study is to investigate the effects of NiNPs on the methionine sulfoxide reductases (MSR) protein repairing system.
Two physically similar nickel-based nanoparticles, NiNPs and carbon-coated NiNP (C-NiNPs; control particles), were exposed to human epithelial A549 cells. Cell viability, benzo(a)pyrene diolepoxide (BPDE) protein adducts, methionine oxidation, MSRA and B3, microtubule-associated protein 1A/1B-light chain 3 (LC3) and extracellular signal-regulated kinase (ERK) phosphorylation were investigated.
Exposure to NiNPs led to a dose-dependent reduction in cell viability and increased BPDE protein adduct production and methionine oxidation. The methionine repairing enzymatic MSRA and MSRB3 production were suppressed in response to NiNP exposure, suggesting the oxidation of methionine to MetO by NiNP was not reversed back to methionine. Additionally, LC3, an autophagy marker, was down-regulated by NiNPs. Both NiNP and C-NiNP caused ERK phosphorylation. LC3 was positively correlated with MSRA (r = 0.929, p < 0.05) and MSRB3 (r = 0.893, p < 0.05).
MSR was made aberrant by NiNP, which could lead to the dysfunction of autophagy and ERK phosphorylation. The toxicological consequences may be dependent on the chemical characteristics of the nanoparticles.
蛋白质氧化被认为是细胞死亡的主要原因之一，而甲硫氨酸是活性氧（ROS）的主要作用靶点之一。然而，镍纳米颗粒（NiNPs）对蛋白质造成氧化损伤的机制仍不清楚。
本研究旨在探究NiNPs对甲硫氨酸亚砜还原酶（MSR）蛋白质修复系统的影响。
将两种物理性质相似的镍基纳米颗粒，即NiNPs和碳包覆NiNP（C-NiNPs；对照颗粒）暴露于人类上皮A549细胞。研究细胞活力、苯并(a)芘二环氧物（BPDE）蛋白质加合物、甲硫氨酸氧化、MSRA和B3、微管相关蛋白1A/1B轻链3（LC3）以及细胞外信号调节激酶（ERK）磷酸化情况。
暴露于NiNPs导致细胞活力呈剂量依赖性降低，BPDE蛋白质加合物生成增加以及甲硫氨酸氧化。响应NiNP暴露，甲硫氨酸修复酶MSRA和MSRB3的生成受到抑制，这表明NiNP将甲硫氨酸氧化为甲硫氨酸亚砜（MetO）后无法再还原为甲硫氨酸。此外，自噬标志物LC3被NiNPs下调。NiNP和C-NiNP均引起ERK磷酸化。LC3与MSRA呈正相关（r = 0.929，p < 0.05），与MSRB3也呈正相关（r = 0.893，p < 0.05）。
NiNP使MSR异常化，这可能导致自噬功能障碍和ERK磷酸化。毒理学后果可能取决于纳米颗粒的化学特性。
