title: Functional characterization of naturally occurring melittin peptide isoforms in two honey bee species, Apis mellifera and Apis cerana.
abstract: Insect-derived antimicrobial peptides (AMPs) have diverse effects on antimicrobial properties and pharmacological activities such as anti-inflammation and anticancer properties. Naturally occurring genetic polymorphism have a direct and/or indirect influence on pharmacological effect of AMPs, therefore information on single nucleotide polymorphism (SNP) occurring in natural AMPs provides an important clue to therapeutic applications. Here we identified nucleotide polymorphisms in melittin gene of honey bee populations, which is one of the potent AMP in bee venoms. We found that the novel SNP of melittin gene exists in these two honey bee species, Apis mellifera and Apis cerana. Nine polymorphisms were identified within the coding region of the melittin gene, of which one polymorphism that resulted in serine (Ser) to asparagine (Asp) substitution that can potentially effect on biological activities of melittin peptide. Serine-substituted melittin (Mel-S) showed more cytotoxic effect than asparagine-substituted melittin (Mel-N) against E. coli. Also, Mel-N and Mel-S had different inhibitory effects on the production of inflammatory factors such as IL-6 and TNF-α in BV-2 cells. Moreover, Mel-S showed stronger cytotoxic activities than Mel-N peptide against two human ovarian cancer cell lines. Using carbon nanotube-based transistor, we here characterized that Mel-S interacted with small unilamellar liposomes more strongly than Mel-N. Taken together, our present study demonstrates that there exist different characteristics of the gene frequency and the biological activities of the melittin peptide in two honey bee species, Apis mellifera and A. cerana.
authors: WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture & Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors: Doori
authors: D
authors: Park
authors: WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture & Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors: Je Won
authors: JW
authors: Jung
authors: Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843, United States.
authors: Mi Ok
authors: MO
authors: Lee
authors: WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture & Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors: Si Young
authors: SY
authors: Lee
authors: WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture & Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors: Boyun
authors: B
authors: Kim
authors: Department of Physics and Astronomy, Seoul National University, Seoul 151-747, Republic of Korea.
authors: Hye Jun
authors: HJ
authors: Jin
authors: WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture & Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors: Jiyoung
authors: J
authors: Kim
authors: WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture & Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors: Young-Joon
authors: YJ
authors: Ahn
authors: WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture & Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors: Ki Won
authors: KW
authors: Lee
authors: WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture & Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors: Yong Sang
authors: YS
authors: Song
authors: Department of Physics and Astronomy, Seoul National University, Seoul 151-747, Republic of Korea.
authors: Seunghun
authors: S
authors: Hong
authors: Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843, United States.
authors: James E
authors: JE
authors: Womack
authors: WCU Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture & Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea. Electronic address: biomodeling@snu.ac.kr.
authors: Hyung Wook
authors: HW
authors: Kwon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D001483:Base Sequence; D001516:Bees; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008555:Melitten / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D020033:Protein Isoforms; D008555:Melitten
keywords: Anti-cancer activity; Anti-inflammatory effect; Antimicrobial peptide (AMP); Honey bee; Melittin; Single nucleotide polymorphism (SNP)