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Protective effects of melittin on tumor necrosis factor-α induced hepatic damage through suppression of apoptotic pathway and nuclear factor-kappa B activation.

Abstract

Melittin, a major polypeptide in honeybee venom, have been used to treat inflammatory disease. Various studies have demonstrated the anti-bacterial, anti-viral, anti-inflammatory and anticancer effects of bee venom and melittin. However, the precise mechanism of melittin in liver disease is not yet known. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis. In the present study, we investigated the anti-apoptotic effect of melittin on tumor necrosis factor (TNF)-α/actinomycin (Act) D-induced apoptosis in hepatocytes. Our results show significant protection from DNA damage by melittin treatment compared with corresponding TNF-α/Act D-treated hepatocytes without melittin. Melittin inhibited TNF-α/Act D-induced activation of the caspase, bcl-2 family of proteins and poly ADP-ribose polymerase (PARP)-1. Our results also indicate that melittin decreased nuclear factor-kappa B (NF-κB) by degradation of phosphorylation of IκB kinase (p-IKK) and NF-κB DNA binding activity in TNF-α/Act D-treated hepatocytes. These results suggest that melittin possesses a potent suppressive effect on apoptotic responses in TNF-α/Act D-treated hepatocytes via the NF-κB pathway.

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  • Authors+Show Affiliations

    ,

    Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu 705-718, Republic of Korea.

    ,

    Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu 705-718, Republic of Korea.

    ,

    Department of Microbiology, Keimyung University, College of Natural Science, Daegu 704-701, Republic of Korea.

    ,

    Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon 441-100, Republic of Korea.

    ,

    Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu 705-718, Republic of Korea.

    Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu 705-718, Republic of Korea kkpark@cu.ac.kr.

    Source

    MeSH

    Animals
    Apoptosis
    Cell Line
    Dactinomycin
    Hepatocytes
    Immunologic Factors
    Melitten
    Mice
    NF-kappa B
    Tumor Necrosis Factor-alpha

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    24872433

    Citation

    Park, Ji-Hyun, et al. "Protective Effects of Melittin On Tumor Necrosis Factor-α Induced Hepatic Damage Through Suppression of Apoptotic Pathway and Nuclear Factor-kappa B Activation." Experimental Biology and Medicine (Maywood, N.J.), vol. 239, no. 12, 2014, pp. 1705-14.
    Park JH, Lee WR, Kim HS, et al. Protective effects of melittin on tumor necrosis factor-α induced hepatic damage through suppression of apoptotic pathway and nuclear factor-kappa B activation. Exp Biol Med (Maywood). 2014;239(12):1705-14.
    Park, J. H., Lee, W. R., Kim, H. S., Han, S. M., Chang, Y. C., & Park, K. K. (2014). Protective effects of melittin on tumor necrosis factor-α induced hepatic damage through suppression of apoptotic pathway and nuclear factor-kappa B activation. Experimental Biology and Medicine (Maywood, N.J.), 239(12), pp. 1705-14. doi:10.1177/1535370214533880.
    Park JH, et al. Protective Effects of Melittin On Tumor Necrosis Factor-α Induced Hepatic Damage Through Suppression of Apoptotic Pathway and Nuclear Factor-kappa B Activation. Exp Biol Med (Maywood). 2014;239(12):1705-14. PubMed PMID: 24872433.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Protective effects of melittin on tumor necrosis factor-α induced hepatic damage through suppression of apoptotic pathway and nuclear factor-kappa B activation. AU - Park,Ji-Hyun, AU - Lee,Woo-Ram, AU - Kim,Hyun-Soo, AU - Han,Sang-Mi, AU - Chang,Young-Chae, AU - Park,Kwan-Kyu, Y1 - 2014/05/28/ PY - 2014/5/30/entrez PY - 2014/5/30/pubmed PY - 2015/2/11/medline KW - Melittin KW - apoptosis KW - hepatocyte KW - nuclear factor-kappa B KW - tumor necrosis factor-α SP - 1705 EP - 14 JF - Experimental biology and medicine (Maywood, N.J.) JO - Exp. Biol. Med. (Maywood) VL - 239 IS - 12 N2 - Melittin, a major polypeptide in honeybee venom, have been used to treat inflammatory disease. Various studies have demonstrated the anti-bacterial, anti-viral, anti-inflammatory and anticancer effects of bee venom and melittin. However, the precise mechanism of melittin in liver disease is not yet known. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis. In the present study, we investigated the anti-apoptotic effect of melittin on tumor necrosis factor (TNF)-α/actinomycin (Act) D-induced apoptosis in hepatocytes. Our results show significant protection from DNA damage by melittin treatment compared with corresponding TNF-α/Act D-treated hepatocytes without melittin. Melittin inhibited TNF-α/Act D-induced activation of the caspase, bcl-2 family of proteins and poly ADP-ribose polymerase (PARP)-1. Our results also indicate that melittin decreased nuclear factor-kappa B (NF-κB) by degradation of phosphorylation of IκB kinase (p-IKK) and NF-κB DNA binding activity in TNF-α/Act D-treated hepatocytes. These results suggest that melittin possesses a potent suppressive effect on apoptotic responses in TNF-α/Act D-treated hepatocytes via the NF-κB pathway. SN - 1535-3699 UR - https://www.unboundmedicine.com/medline/citation/24872433/Protective_effects_of_melittin_on_tumor_necrosis_factor_α_induced_hepatic_damage_through_suppression_of_apoptotic_pathway_and_nuclear_factor_kappa_B_activation_ L2 - http://journals.sagepub.com/doi/full/10.1177/1535370214533880?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -