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Nickel oxide nanoparticles induce hepatocyte apoptosis via activating endoplasmic reticulum stress pathways in rats
Author(s) -
Chang Xuhong,
Liu Fangfang,
Tian Minmin,
Zhao Hongjun,
Han Aijie,
Sun Yingbiao
Publication year - 2017
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22492
Subject(s) - unfolded protein response , endoplasmic reticulum , apoptosis , hepatocyte , tunel assay , glucose regulated protein , microbiology and biotechnology , signal transduction , chemistry , biology , biochemistry , in vitro
Nickel oxide nanoparticles (nano NiO) could induce hepatocyte apoptosis, while its potential mechanisms are unclear. This study aimed to explore the role of endoplasmic reticulum (ER) stress pathways in hepatocyte apoptosis induced by nano NiO. Male Wistar rats were administrated with nano NiO (0.015, 0.06, and 0.24 mg/kg b.w.) and micro NiO (0.24 mg/kg b.w.) by intratracheal instillation twice a week for 6 weeks. We measured the hepatocyte apoptosis levels by TdT‐mediated dUTP nick‐end labeling (TUNEL) staining, ER stress related gene and protein expression levels in rat liver. The results showed that the TUNEL positive cells increased after exposure nano NiO, hinting hepatocyte apoptosis. The up‐regulated gene and protein levels of 78 kD glucose regulated protein and CCAAT/enhancer binding protein homologous protein suggested that nano NiO triggered ER stress. Nano NiO exposure contributed to the increased protein contents of inositol‐requiring enzyme 1 (IRE‐1)α, p‐IRE‐1α, X box protein‐1S, pancreatic ER kinase (PERK), p‐PERK, eukaryotic initiation factor‐2 alpha (eIF‐2α), p‐eIF‐2α, caspase‐12, −9, and −3, implicating that nano NiO can activate the pathways of ER stress‐mediated apoptosis. These findings indicate that the ER stress pathways may play an important role in hepatocyte apoptosis induced by nano NiO.