Neurotropic and neuroprotective activities of the earthworm peptide Lumbricusin

• Published in: Biochemical and biophysical research communications 2014-06, Vol.448 (3), p.292-297
• Main Authors: Kim, Dae Hong, Lee, Ik Hwan, Nam, Seung Taek, Hong, Ji, Zhang, Peng, Hwang, Jae Sam, Seok, Heon, Choi, Hyemin, Lee, Dong Gun, Kim, Jae Il, Kim, Ho
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; AMINO ACID SEQUENCE; Animals; ANNELIDS; Anti-apoptotic activity; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - isolation & purification; Antimicrobial Cationic Peptides - pharmacology; APOPTOSIS; Apoptosis - drug effects; BEETLES; BROMIDES; CELL CYCLE; Cell cycle arrest; Cell Line; CELL PROLIFERATION; Cell proliferation (neurotropine); Cell Proliferation - drug effects; Cell Survival - drug effects; Cyclin-Dependent Kinase Inhibitor p27 - genetics; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; DISEASES; DMSO; DOPAMINE; Earthworm peptide; FLUORESCENCE; Helminth Proteins - genetics; Helminth Proteins - isolation & purification; Helminth Proteins - pharmacology; HUMAN POPULATIONS; Humans; MONOCLINIC LATTICES; Neurogenesis - drug effects; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuroprotective activity; Neuroprotective Agents - chemistry; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; Oligochaeta - chemistry; Oligochaeta - genetics; Oxidopamine - antagonists & inhibitors; Oxidopamine - toxicity; Parkinson Disease - drug therapy; POLYPEPTIDES; Proteasomal protein degradation; Proteasome Endopeptidase Complex - metabolism; Proteolysis - drug effects; TIME DEPENDENCE; VIABILITY
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.04.105

•11-mer peptide Lumbricusin, a defensin like peptide, is isolated from earthworm.•We here demonstrated that Lumbricusin has neurotropic and neuroprotective effects.•p27 degradation by Lumbricusin mediates effects of Lumbricusin on neuronal cells. 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 p27Kip1 protein, a negative regulator of cell-cycle progression, in SH-SY5Y cells, and markedly promoted its degradation. Notably, adenoviral-mediated over-expression of p27Kip1 significantly blocked the antiapoptotic effect of Lumbricusin in 6-hydroxy dopamine-treated SH-SY5Y cells. These results suggest that promotion of p27Kip1 degradation may be the main mechanism underlying the neuroprotective and neurotropic effects of Lumbricusin.