title: Neurotropic and neuroprotective activities of the earthworm peptide Lumbricusin.
abstract: We recently isolated a polypeptide from the earthworm Lumbricus terrestris that is structurally similar to defensin, a well-known antibacterial peptide. An 11-mer antibacterial peptide (NH2-RNRRWCIDQQA), designated Lumbricusin, was synthesized based on the amino acid sequence of the isolated polypeptide. Since we previously reported that CopA3, a dung beetle peptide, enhanced neuronal cell proliferation, we here examined whether Lumbricusin exerted neurotropic and/or neuroprotective effects. Lumbricusin treatment induced a time-dependent increase (∼51%) in the proliferation of human neuroblastoma SH-SY5Y cells. Lumbricusin also significantly inhibited the apoptosis and decreased viability induced by treatment with 6-hydroxy dopamine, a Parkinson's disease-mimicking agent. Immunoblot analyses revealed that Lumbricusin treatment increased ubiquitination of p27(Kip1) protein, a negative regulator of cell-cycle progression, in SH-SY5Y cells, and markedly promoted its degradation. Notably, adenoviral-mediated over-expression of p27(Kip1) significantly blocked the antiapoptotic effect of Lumbricusin in 6-hydroxy dopamine-treated SH-SY5Y cells. These results suggest that promotion of p27(Kip1) degradation may be the main mechanism underlying the neuroprotective and neurotropic effects of Lumbricusin.
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711, South Korea.
authors.forename: Dae Hong
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711, South Korea.
authors.forename: Ik Hwan
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711, South Korea.
authors.forename: Seung Taek
authors.initials: ST
authors.lastname: Nam
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711, South Korea.
authors.forename: Ji
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711, South Korea.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-707, South Korea.
authors.forename: Jae Sam
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: Department of Biomedical Engineering, Jungwon University, Goesan, Chungcheongbukdo 367-700, South Korea.
authors.forename: Heon
authors.initials: H
authors.lastname: Seok
authors.affiliation: School of Life Sciences, KNU Creative Bioresearch Group (BK21 Plus Program), College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, South Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Choi
authors.affiliation: School of Life Sciences, KNU Creative Bioresearch Group (BK21 Plus Program), College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, South Korea.
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712, South Korea.
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711, South Korea. Electronic address: hokim@daejin.ac.kr.
authors.forename: Ho
authors.initials: H
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015801:Helminth Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D009835:Oligochaeta / Q000737:chemistry* / Q000235:genetics; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects
chemical_list: D023181:Antimicrobial Cationic Peptides; C436291:CDKN1B protein, human; D015801:Helminth Proteins; D018696:Neuroprotective Agents; C000590837:lumbricusin peptide, Lumbricus terrestris; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016627:Oxidopamine; D046988:Proteasome Endopeptidase Complex
keywords: Anti-apoptotic activity; Cell cycle arrest; Cell proliferation (neurotropine); Earthworm peptide; Neuroprotective activity; Proteasomal protein degradation