Parkin suppresses wild-type alpha-synuclein-induced toxicity in SHSY-5Y cells.
Current hypotheses concerning the mechanism of neuronal cell death in Parkinson's disease (PD) and related synucleopathies propose a functional interaction between parkin and alpha-synuclein (alphaS). Recently parkin was shown to suppress mutant alphaS-induced toxicity in primary neurons, providing a basis for an association between these proteins and neuronal loss [Neuron 36 (2000) 1007-1019]. We have asked if a similar association could be made between wild-type (wt) alphaS and parkin. We examined inducible over-expression of alphaS in SHSY-5Y cells through adenoviral infection under conditions which produce cellular toxicity through a reduction in ATP levels. We demonstrate that parkin suppresses toxicity induced by mutant (A53T) and wt alphaS. Parkin over-expression was also associated with the appearance of higher molecular weight alphaS-immunoreactive bands by Western blot analysis. These data, consistent with a protective role for parkin, extend previous findings to include a functional association between parkin and the wt form of alphaS.
Oluwatosin-Chigbu
Yemisi
Y
Department of Molecular Science, AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, Wilmington, DE 19850-5437, USA.
Robbins
Alan
A
Scott
Clay W
CW
Arriza
Jeffrey L
JL
Reid
John D
JD
Zysk
John R
JR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival; D019610:Cytoprotection; D015870:Gene Expression; D005822:Genetic Vectors; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051843:Synucleins; D014162:Transfection; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D051843:Synucleins; D051844:alpha-Synuclein; D000255:Adenosine Triphosphate; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases