title: Insect peptide CopA3-induced protein degradation of p27Kip1 stimulates proliferation and protects neuronal cells from apoptosis.
abstract: We recently demonstrated that the antibacterial peptide, CopA3 (a D-type disulfide dimer peptide, LLCIALRKK), inhibits LPS-induced macrophage activation and also has anticancer activity in leukemia cells. Here, we examined whether CopA3 could affect neuronal cell proliferation. We found that CopA3 time-dependently increased cell proliferation by up to 31 ± 2% in human neuroblastoma SH-SY5Y cells, and up to 29 ± 2% in neural stem cells isolated from neonatal mouse brains. In both cell types, CopA3 also significantly inhibited the apoptosis and viability losses caused by 6-hydroxy dopamine (a Parkinson disease-mimicking agent) and okadaic acid (an Alzheimer's disease-mimicking agent). Immunoblotting revealed that the p27Kip1 protein (a negative regulator of cell cycle progression) was markedly degraded in CopA3-treated SH-SY5Y cells. Conversely, an adenovirus expressing p27Kip1 significantly inhibited the antiapoptotic effects of CopA3 against 6-hydroxy dopamine- and okadaic acid-induced apoptosis, and decreased the neurotropic effects of CopA3. These results collectively suggest that CopA3-mediated protein degradation of p27Kip1 may be the main mechanism through which CopA3 exerts neuroprotective and neurotropic effects.
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.forename: Dae Hong
authors.initials: DH
authors.lastname: Kim
authors.forename: Min Bum
authors.initials: MB
authors.lastname: Lee
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Nam
authors.forename: Jin Ku
authors.initials: JK
authors.lastname: Kang
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Ik Hwan
authors.initials: IH
authors.lastname: Lee
authors.forename: Heon
authors.initials: H
authors.lastname: Seok
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
authors.forename: Jae Sam
authors.initials: JS
authors.lastname: Hwang
authors.forename: Ho
authors.initials: H
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D001517:Coleoptera / Q000737:chemistry*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects*
chemical_list: D023181:Antimicrobial Cationic Peptides; C583724:CopA3 peptide, Copris tripartitus; D019476:Insect Proteins; D018696:Neuroprotective Agents; D010455:Peptides; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019319:Okadaic Acid; D016627:Oxidopamine
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; 6-OHDA; 6-hydroxy dopamine; Apoptosis; Caspase-3; Cell proliferation; Cell viability; Insect peptide; MNSCs; MTT; Mouse neural stem cells; Neuronal cells; Neuroprotective activity; Neurotropic factor; OA; mouse neural stem cells; okadaic acid; p27Kip1