Cu-induced mitochondrial dysfunction is mediated by abnormal mitochondrial fission through oxidative stress in primary chicken embryo hepatocytes

Background: Excess copper (Cu) is an oxidative stress factor which associates with a variety of diseases. The aim of this study was to evaluate the effect of Cu in primary chicken embryo hepatocytes (CEHs). Methods: CEHs were isolated from 13 days old chicken embryos and followed by different concentration Cu (0, 10, 100, 200 ?M) and/or ALC treatment (0.3 mg/mL) for 12 or 24 h. The effects of Cu exposure in CEHs were determined by detecting reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (MMP), and ATP levels. The expression of mitochondrial dynamics-related genes and proteins were also detected. Results: Results showed that Cu treatment (100 or 200 ?M) significantly decreased CEHs viability, MMP and ATP levels, increased ROS and MDA levels in 12 or 24 h. The up-regulated mitochondrial fission genes and protein in 100 and 200 ?M Cu groups suggested Cu promoted mitochondrial division but not fusion. However, the cotreatment of ALC and Cu alleviated those changes compared with the 100 or 200 ?M Cu groups. Conclusion: In conclusion, we speculated that Cu increased the oxidative stress and induced mitochondria dysfunction via disturbing mitochondrial dynamic balance in CEHs, and this process was not completely reversible.

Automated summary

The study found that exposure to Cu in primary chicken embryo hepatocytes can lead to oxidative stress and mitochondrial dysfunction, which may be irreversible.