Protective effects of melittin on transforming growth factor-{beta}1 injury to hepatocytes via anti-apoptotic mechanism

Journal Article · Sat Oct 15 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.08.012· OSTI ID:21587866

Lee, Woo-Ram; Park, Ji-Hyun; Kim, Kyung-Hyun ^[1]; Park, Yoon-Yub ^[2]; Han, Sang-Mi ^[3]; Park, Kwan-kyu ^[1]

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1. Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu (Korea, Republic of)
2. Department of Physiology, College of Medicine, Catholic University of Daegu, Daegu (Korea, Republic of)
3. Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon (Korea, Republic of)

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)-{beta}1-induced apoptosis in hepatocytes. TGF-{beta}1-treated hepatocytes were exposed to low doses (0.5 and 1 {mu}g/mL) and high dose (2 {mu}g/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-{beta}1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-{beta}1-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-{beta}1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-{beta}1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-{beta}1-mediated injury. - Highlights: > We investigated the anti-apoptotic effect of melittin on TGF-{beta}1-induced hepatocyte. > TGF-{beta}1 induces hepatocyte apoptosis. > TGF-{beta}1-treated hepatocytes were exposed to low doses and high dose of melittin. > Optimal dose of melittin exerts anti-apoptotic effects to hepatocytes.

• OSTI ID: 21587866
• Journal Information: Toxicology and Applied Pharmacology, Vol. 256, Issue 2; Other Information: DOI: 10.1016/j.taap.2011.08.012; PII: S0041-008X(11)00310-3; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
BEES
DNA DAMAGES
DOSES
FIBROSIS
GROWTH FACTORS
INFLAMMATION
INJURIES
LIVER
LIVER CELLS
NEOPLASMS
PEPTIDES
RIBOSE
TOXICITY
ALDEHYDES
ANIMAL CELLS
ANIMALS
ARTHROPODS
BODY
CARBOHYDRATES
DIGESTIVE SYSTEM
DISEASES
GLANDS
HYMENOPTERA
INSECTS
INVERTEBRATES
MITOGENS
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PENTOSES
PROTEINS
SACCHARIDES
SOMATIC CELLS
SYMPTOMS