Synphilin-1 exhibits trophic and protective effects against Rotenone toxicity.
Synphilin-1 is a cytoplasmic protein with unclear function. Synphilin-1 has been identified as an interaction partner of alpha-synuclein. The interaction between synphilin-1 and alpha-synuclein has implications in Parkinson's disease. In this study, we stably overexpressed human synphilin-1 in mouse N1E-115 neuroblastoma cells. We found that overexpression of synphilin-1 shortened cell growth doubling time and increased neurite outgrowth. Knockdown of endogenous synphilin-1 caused neuronal toxicity and shortened neurite outgrowth. We further found that synphilin-1 increased activation of the extracellular signal-regulated kinases (ERK1/2) and mediated neurite outgrowth. Rotenone, mitochondrial complex I inhibitor, has been shown previously to induce dopaminergic neurodegeneration and Parkinsonism in rats and Drosophila. We found that Rotenone induced apoptotic cell death in N1E-115 cells via caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage. Overexpression of synphilin-1 significantly reduced Rotenone-induced cell death, caspase-3 activation and PARP cleavage. The results indicate that synphilin-1 displays trophic and protective effects in vitro, suggesting that synphilin-1 may play a protective role in Parkinson's disease (PD) pathogenesis and may lead to a potential therapeutic target for PD intervention.
Li
X
X
Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, PR China.
Liu
Z
Z
Tamashiro
K
K
Shi
B
B
Rudnicki
D D
DD
Ross
C A
CA
Moran
T H
TH
Smith
W W
WW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D049108:Cell Enlargement; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C118958:SNCAIP protein, human; C498464:Sncaip protein, mouse; D012402:Rotenone; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C505409:Casp3 protein, mouse; D053148:Caspase 3; D042967:Electron Transport Complex I