title: 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.
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, South Korea.
authors.forename: Woo-Ram
authors.initials: WR
authors.lastname: Lee
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Yoon-Yub
authors.initials: YY
authors.lastname: Park
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Han
authors.forename: Kwan-kyu
authors.initials: KK
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000096:biosynthesis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000517:prevention & control*; D045304:Cytochromes c / Q000096:biosynthesis; D005434:Flow Cytometry; D022781:Hepatocytes / Q000187:drug effects*; D015151:Immunoblotting; D008555:Melitten / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D053773:Transforming Growth Factor beta1; D008555:Melitten; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases