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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

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Abstract

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.

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Acknowledgements

Not applicable.

Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded by the Korea government (2019R1F1A105809412).

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Authors and Affiliations

  1. Cheong-Choon Korean Medical Clinic, 47388, Busan, Republic of Korea

    Hyeon-Gyun Jo

  2. Department of Biochemistry, Dong-eui University College of Korean Medicine, 47227, Busan, Republic of Korea

    Hyeon-Gyun Jo, Hyesook Lee, Yung Hyun Choi & Su Hyun Hong

  3. Division of Basic Sciences, College of Liberal Studies, Dong-eui University, 47340, Busan, Republic of Korea

    Cheol Park

  4. Anti-Aging Research Center, Dong‐eui University, 47340, Busan, Republic of Korea

    Hyesook Lee, Yung Hyun Choi & Su Hyun Hong

  5. Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, 63243, Jeju, Republic of Korea

    Gi-Young Kim

  6. College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, 10326, Goyang, Republic of Korea

    Young-Sam Keum

  7. Department of Biochemistry, College of Medicine, Jeju National University, 63243, Jeju, Republic of Korea

    Jin Won Hyun

  8. Department of Immunology, School of Medicine, Keimyung University, 42601, Daegu, Republic of Korea

    Taeg Kyu Kwon

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  1. Hyeon-Gyun Jo
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Contributions

H-GJ, YHC and SHH designed the research; H-GJ, CP, HL, G-YK, SHC, JWH. KTK and Y-SK conducted the experiments, interpreted the results. YHC and SHH wrote and finalized the manuscript.

Corresponding authors

Correspondence to Yung Hyun Choi or Su Hyun Hong.

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Jo, HG., Park, C., Lee, H. et al. 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 Genom 43, 17–31 (2021). https://doi.org/10.1007/s13258-020-01018-3

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