Document Detail

RA410/Sly1 suppresses MPP+ and 6-hydroxydopamine-induced cell death in SH-SY5Y cells.
MedLine Citation:
PMID:  15649705     Owner:  NLM     Status:  MEDLINE    
Parkinson's disease is characterized by selective loss of dopaminergic neurons in the substantia nigra. However, its associated cell death mechanism remains unknown. 1-Methyl-4-phenil-pyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) cause dopaminergic neuronal cell death. Both are widely used to model PD. We investigated the role of a vesicle-transport-related protein, RA410/Sly1, in SH-SY5Y cells to clarify the mechanism of cellular adaptation to MPP+ and 6-OHDA-induced stress. Antisense RA410/Sly1 transformants treated with these toxins displayed reduced viability in comparison with viability of wild-type or RA410/Sly1 sense transformants. Electron microscopy analysis indicated that the ER in MPP+-treated antisense RA410/Sly1 transformants was rapidly disrupted in comparison to wild-type or sense RNA transformants. Cell death induced by MPP+ and 6-OHDA was suppressed in RA410/Sly1 sense transformants through suppression of caspase-2, -3 and -9 activation. These results suggest that RA410/Sly1 plays an important cytoprotective role in MPP+ and 6-OHDA-induced cellular perturbation.
Yoshio Bando; Taiichi Katayama; Manabu Taniguchi; Tomohiko Ishibashi; Noriyuki Matsuo; Satoshi Ogawa; Masaya Tohyama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurobiology of disease     Volume:  18     ISSN:  0969-9961     ISO Abbreviation:  Neurobiol. Dis.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-14     Completed Date:  2005-05-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  143-51     Citation Subset:  IM    
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
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MeSH Terms
1-Methyl-4-phenylpyridinium / toxicity
Adaptation, Physiological / physiology
Apoptosis / drug effects,  physiology*
Carrier Proteins / antagonists & inhibitors,  genetics,  physiology*
Caspases / metabolism
Cell Survival / drug effects,  physiology
Dopamine / metabolism
Endoplasmic Reticulum / drug effects,  pathology,  ultrastructure
Immediate-Early Proteins / antagonists & inhibitors,  genetics,  physiology*
Microscopy, Electron, Transmission
Munc18 Proteins
Nerve Degeneration / chemically induced,  metabolism*,  pathology
Neurons / drug effects,  pathology,  ultrastructure
Neurotoxins / toxicity*
Oligonucleotides, Antisense / pharmacology
Oxidative Stress / drug effects,  physiology*
Oxidopamine / toxicity
Parkinsonian Disorders / chemically induced,  metabolism,  pathology
Substantia Nigra / drug effects,  pathology,  physiopathology
Tumor Cells, Cultured
Reg. No./Substance:
0/Carrier Proteins; 0/Immediate-Early Proteins; 0/Munc18 Proteins; 0/Neurotoxins; 0/Oligonucleotides, Antisense; 0/Scfd1 protein, rat; 1199-18-4/Oxidopamine; 48134-75-4/1-Methyl-4-phenylpyridinium; EC 3.4.22.-/Caspases

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