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Protective effects of melittin on transforming growth factor-β1 injury to hepatocytes via anti-apoptotic mechanism.

Abstract

Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated in hepatocytes. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis, portal hypertension, liver cancer, and other liver diseases. In the present study, we investigated the anti-apoptotic effect of melittin on transforming growth factor (TGF)-β1-induced apoptosis in hepatocytes. TGF-β1-treated hepatocytes were exposed to low doses (0.5 and 1 μg/mL) and high dose (2 μg/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-β1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-β1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase (PARP) cleavage. These results demonstrate that TGF-β1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-β1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-β1-mediated injury.

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  • Authors+Show Affiliations

    ,

    Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, South Korea.

    , , , ,

    Source

    Toxicology and applied pharmacology 256:2 2011 Oct 15 pg 209-15

    MeSH

    Animals
    Apoptosis
    Caspases
    Cell Line
    Cell Survival
    Chemical and Drug Induced Liver Injury
    Cytochromes c
    Flow Cytometry
    Hepatocytes
    Immunoblotting
    Melitten
    Membrane Potential, Mitochondrial
    Mice
    Mitochondria, Liver
    Poly(ADP-ribose) Polymerases
    Proto-Oncogene Proteins c-bcl-2
    Transforming Growth Factor beta1

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21871910

    Citation

    Lee, Woo-Ram, et al. "Protective Effects of Melittin On Transforming Growth Factor-β1 Injury to Hepatocytes Via Anti-apoptotic Mechanism." Toxicology and Applied Pharmacology, vol. 256, no. 2, 2011, pp. 209-15.
    Lee WR, Park JH, Kim KH, et al. Protective effects of melittin on transforming growth factor-β1 injury to hepatocytes via anti-apoptotic mechanism. Toxicol Appl Pharmacol. 2011;256(2):209-15.
    Lee, W. R., Park, J. H., Kim, K. H., Park, Y. Y., Han, S. M., & Park, K. K. (2011). Protective effects of melittin on transforming growth factor-β1 injury to hepatocytes via anti-apoptotic mechanism. Toxicology and Applied Pharmacology, 256(2), pp. 209-15. doi:10.1016/j.taap.2011.08.012.
    Lee WR, et al. Protective Effects of Melittin On Transforming Growth Factor-β1 Injury to Hepatocytes Via Anti-apoptotic Mechanism. Toxicol Appl Pharmacol. 2011 Oct 15;256(2):209-15. PubMed PMID: 21871910.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Protective effects of melittin on transforming growth factor-β1 injury to hepatocytes via anti-apoptotic mechanism. AU - Lee,Woo-Ram, AU - Park,Ji-Hyun, AU - Kim,Kyung-Hyun, AU - Park,Yoon-Yub, AU - Han,Sang-Mi, AU - Park,Kwan-kyu, Y1 - 2011/08/17/ PY - 2011/07/22/received PY - 2011/08/10/revised PY - 2011/08/10/accepted PY - 2011/8/30/entrez PY - 2011/8/30/pubmed PY - 2011/12/13/medline SP - 209 EP - 15 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 256 IS - 2 N2 - Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated in hepatocytes. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis, portal hypertension, liver cancer, and other liver diseases. In the present study, we investigated the anti-apoptotic effect of melittin on transforming growth factor (TGF)-β1-induced apoptosis in hepatocytes. TGF-β1-treated hepatocytes were exposed to low doses (0.5 and 1 μg/mL) and high dose (2 μg/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-β1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-β1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase (PARP) cleavage. These results demonstrate that TGF-β1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-β1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-β1-mediated injury. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/21871910/Protective_effects_of_melittin_on_transforming_growth_factor_β1_injury_to_hepatocytes_via_anti_apoptotic_mechanism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(11)00310-3 DB - PRIME DP - Unbound Medicine ER -