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Inhibition of oxidative stress induced-cytotoxicity by coptisine in V79-4 Chinese hamster lung fibroblasts through the induction of Nrf-2 mediated HO-1 expression
Genes & Genomics ( IF 1.6 ) Pub Date : 2020-11-25 , DOI: 10.1007/s13258-020-01018-3
Hyeon-Gyun Jo 1, 2 , Cheol Park 3 , Hyesook Lee 2, 4 , Gi-Young Kim 5 , Young-Sam Keum 6 , Jin Won Hyun 7 , Taeg Kyu Kwon 8 , Yung Hyun Choi 2, 4 , Su Hyun Hong 2, 4
Affiliation  

Background

Coptisine is a natural alkaloid compound and is known to have multiple beneficial effects including antioxidant activity. However, whether it can protect lung fibroblasts from oxidative damage has not been studied yet.

Objectives

To investigate the potential inhibitory effect of coptisine against oxidative stress in V79-4 lung fibroblast cells.

Methods

V79-4 cells were treated with H2O2 (1 mM) in the presence or absence of coptisine (50 µg/ml), N-acetyl cysteine (NAC, 10 mM) or zinc protoporphyrin IX (ZnPP, 10 µM) for the indicated times. The alleviating effects of coptisine on cytotoxicity, cell cycle arrest, apoptosis, reactive oxygen species (ROS) production, DNA damage, mitochondrial dynamics, and inhibition of ATP production against H2O2 were investigated. Western blot analysis was used to analyze the expression levels of specific proteins.

Results

Coptisine inhibited H2O2-induced cytotoxicity and DNA damage by blocking abnormal ROS generation. H2O2 treatment caused cell cycle arrest at the G2/M phase accompanied by increased expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1 and decreased expression of cyclin B1 and cyclin A. However, these effects were attenuated in the presence of coptisine or NAC. Coptisine also prevented apoptosis by decreasing the rate of Bax/Bcl-2 expression in H2O2-stimulated cells and suppressing the loss of mitochondrial membrane potential and the cytosolic release of cytochrome c. In addition, the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was markedly promoted by coptisine in the presence of H2O2. However, zinc protoporphyrin IX, a potent inhibitor of HO-1, attenuated the ROS scavenging and anti-apoptotic effects of coptisine.

Conclusions

Based on current data, we suggest that coptisine can be used as a potential treatment for oxidative stress-related lung disease.

更新日期:2020-11-25
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