Protective Effects of Nargenicin A1 against Tacrolimus-Induced Oxidative Stress in Hirame Natural Embryo Cells

Cheol Park, Da Hye Kwon, Su Jung Hwang, Min Ho Han, Jin-Woo Jeong, Sang Hoon Hong, Hee-Jae Cha, Su-Hyun Hong, Gi-Young Kim, Hyo-Jong Lee, Suhkmann Kim, Heui-Soo Kim and Yung Hyun Choi
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Cheol Park: Department of Molecular Biology, College of Natural Sciences, Dong-eui University, Busan 47340, Korea
Da Hye Kwon: Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, Korea
Su Jung Hwang: Department of Pharmacy, College of Pharmacy, Inje University, Gimhae 50834, Korea
Min Ho Han: National Marine Biodiversity Institute of Korea, Seocheon 33662, Korea
Jin-Woo Jeong: Nakdonggang National Institute of Biological Resources, Sangju 17104, Korea
Sang Hoon Hong: Department of Internal Medicine, Dong-eui University College of Korean Medicine, Busan 47227, Korea
Hee-Jae Cha: Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Korea
Su-Hyun Hong: Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, Korea
Gi-Young Kim: Department of Marine Life Sciences, Jeju National University, Jeju 63243, Korea
Hyo-Jong Lee: Department of Pharmacy, College of Pharmacy, Inje University, Gimhae 50834, Korea
Suhkmann Kim: Department of Chemistry, College of Natural Sciences, Center for Proteome Biophysics and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Korea
Heui-Soo Kim: Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea
Yung Hyun Choi: Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, Korea

IJERPH, 2019, vol. 16, issue 6, 1-13

Abstract: Tacrolimus is widely used as an immunosuppressant to reduce the risk of rejection after organ transplantation, but its cytotoxicity is problematic. Nargenicin A1 is an antibiotic extracted from Nocardia argentinensis and is known to have antioxidant activity, though its mode of action is unknown. The present study was undertaken to evaluate the protective effects of nargenicin A1 on DNA damage and apoptosis induced by tacrolimus in hirame natural embryo (HINAE) cells. We found that reduced HINAE cell survival by tacrolimus was due to the induction of DNA damage and apoptosis, both of which were prevented by co-treating nargenicin A1 or N-acetyl-l-cysteine, a reactive oxygen species (ROS) scavenger, with tacrolimus. In addition, apoptosis induction by tacrolimus was accompanied by increases in ROS generation and decreases in adenosine triphosphate (ATP) levels caused by mitochondrial dysfunction, and these changes were significantly attenuated in the presence of nargenicin A1, which further indicated tacrolimus-induced apoptosis involved an oxidative stress-associated mechanism. Furthermore, nargenicin A1 suppressed tacrolimus-induced B-cell lymphoma-2 (Bcl-2) down-regulation, Bax up-regulation, and caspase-3 activation. Collectively, these results demonstrate that nargenicin A1 protects HINAE cells against tacrolimus-induced DNA damage and apoptosis, at least in part, by scavenging ROS and thus suppressing the mitochondrial-dependent apoptotic pathway.

Keywords: nargenicin A1; tacrolimus; ROS; DNA damage; apoptosis (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
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