Inhibition of oxidative stress induced-cytotoxicity by coptisine in V79-4 Chinese hamster lung fibroblasts through the i
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Genes & Genomics https://doi.org/10.1007/s13258-020-01018-3
RESEARCH ARTICLE
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 Hyeon‑Gyun Jo1,2 · Cheol Park3 · Hyesook Lee2,4 · Gi‑Young Kim5 · Young‑Sam Keum6 · Jin Won Hyun7 · Taeg Kyu Kwon8 · Yung Hyun Choi2,4 · Su Hyun Hong2,4 Received: 28 September 2020 / Accepted: 5 November 2020 © The Genetics Society of Korea 2020
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 H 2O2 (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 p 21WAF1/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 H 2O2. 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. Keywords Coptisine · ROS · DNA damage · Apoptosis · Nrf2/HO-1
* Yung Hyun Choi [email protected] * Su Hyun Hong [email protected] 1
5
Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, 63243 Jeju, Republic of Korea
6
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, 10326 Goyang, Republic of Korea
Cheong-Choon Korean Medical Clinic, 47388 Busan, Republic of Korea
7
Department of Biochemistry, Dong-eui University College of Korean Medicine, 47227 Busan, Republic of Korea
Department of Biochemistry, College of Medicine, Jeju National
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