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Copper nanoclusters trigger muscle cell apoptosis and atrophy in vitro and in vivo
Author(s) -
Liu Yayun,
Liang Jichao,
Wang Qiuju,
He Yu,
Chen Yong
Publication year - 2016
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3263
Subject(s) - chemistry , c2c12 , myogenesis , apoptosis , lactate dehydrogenase , microbiology and biotechnology , muscle atrophy , in vivo , viability assay , skeletal muscle , medicine , in vitro , endocrinology , biochemistry , biology , enzyme
Copper nanoclusters (CuNCs) are increasingly being used in nanomedicine owing to their utility in cellular imaging and as catalysts. Additionally, nanotoxicology research of CuNCs is gaining attention. We report here the synthesis and characterization of CuNCs and their cytotoxic impact on muscle cells. A simple protein‐directed synthesis of stable CuNCs was prepared, using bovine serum albumin as the stabling agent. Physicochemical characterization of the synthesized CuNCs was performed using transmission electron microscopy. To evaluate the in vitro cytotoxicity, C2C12 cells were exposed to increasing doses (from 0.1 to 50 µg ml –1 ) of CuNCs. CuNCs affected the viability of C2C12 cells in a dose‐dependent manner, as detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and a lactate dehydrogenase release assay. Further studies indicated that CuNCs induced the formation of reactive oxygen species and decreased the activities of catalase and glutathione. CuNC treatment decreased the mitochondrial membrane potential and induced apoptosis, accompanied by an increase in the protein expression ratio of Bax/Bcl‐2 and caspase‐3/9 activity in C2C12 cells. CuNCs treatment resulted in atrophy of the C2C12 myotubes, which was characterized by the increased expression of atrophy‐related genes, such as atrogin‐1 and MuRF1 . Finally, CuNCs induce morphological atrophy of primary muscle cells and mouse gastrocnemius muscle. Taken together, these results suggest that exposure to CuNCs may be a risk factor for the skeletal muscle system. Copyright © 2015 John Wiley & Sons, Ltd.