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

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Listed:
  • 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)

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.

Suggested Citation

  • 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 & Yung Hyun Choi, 2019. "Protective Effects of Nargenicin A1 against Tacrolimus-Induced Oxidative Stress in Hirame Natural Embryo Cells," IJERPH, MDPI, vol. 16(6), pages 1-13, March.
    • Handle: RePEc:gam:jijerp:v:16:y:2019:i:6:p:1044-:d:216443
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    References listed on IDEAS

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    1. Cheol Park & Su Hyun Hong & Soon Shik Shin & Dae-Sung Lee & Min Ho Han & Hee-Jae Cha & Suhkmann Kim & Heui-Soo Kim & Gi-Young Kim & Eui Kyun Park & You-Jin Jeon & Yung Hyun Choi, 2018. "Activation of the Nrf2/HO-1 Signaling Pathway Contributes to the Protective Effects of Sargassum serratifolium Extract against Oxidative Stress-Induced DNA Damage and Apoptosis in SW1353 Human Chondro," IJERPH, MDPI, vol. 15(6), pages 1-13, June.
    2. Toren Finkel & Nikki J. Holbrook, 2000. "Oxidants, oxidative stress and the biology of ageing," Nature, Nature, vol. 408(6809), pages 239-247, November.
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    More about this item

    Keywords

    nargenicin A1; tacrolimus; ROS; DNA damage; apoptosis;
    All these keywords.

    JEL classification:

    • A1 - General Economics and Teaching - - General Economics

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