title: 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.
authors.affiliation: Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Woo-Ram
authors.initials: WR
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Keimyung University, College of Natural Science, Daegu 704-701, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon 441-100, Republic of Korea.
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Han
authors.affiliation: Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Pathology, Catholic University of Daegu, College of Medicine, Daegu 705-718, Republic of Korea kkpark@cu.ac.kr.
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003609:Dactinomycin / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects*; D007155:Immunologic Factors / Q000378:metabolism*; D008555:Melitten / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
chemical_list: D007155:Immunologic Factors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D008555:Melitten
keywords: Melittin; apoptosis; hepatocyte; nuclear factor-kappa B; tumor necrosis factor-α