TY - JOUR
T1 - Dysfunction of methionine sulfoxide reductases to repair damaged proteins by nickel nanoparticles
AU - Feng, Po Hao
AU - Huang, Ya Li
AU - Chuang, Kai Jen
AU - Chen, Kuan Yuan
AU - Lee, Kang Yun
AU - Ho, Shu Chuan
AU - Bien, Mauo Ying
AU - Yang, You Lan
AU - Chuang, Hsiao Chi
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd. All rights reserved.
PY - 2015/5/16
Y1 - 2015/5/16
N2 - Background: 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. Objectives: The objective of this study is to investigate the effects of NiNPs on the methionine sulfoxide reductases (MSR) protein repairing system. Methods: 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. Results: 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). Conclusions: 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.
AB - Background: 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. Objectives: The objective of this study is to investigate the effects of NiNPs on the methionine sulfoxide reductases (MSR) protein repairing system. Methods: 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. Results: 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). Conclusions: 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.
KW - Autophagy
KW - Benzo(a)pyrene diolepoxide protein adduct
KW - Extracellular signal-regulated kinase
KW - Methionine oxidation
KW - Methionine sulfoxide reductases
KW - Nickel nanoparticle
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U2 - 10.1016/j.cbi.2015.05.003
DO - 10.1016/j.cbi.2015.05.003
M3 - Article
C2 - 25979628
AN - SCOPUS:84929303490
SN - 0009-2797
VL - 236
SP - 82
EP - 89
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
ER -