RA410/Sly1 suppresses MPP+ and 6-hydroxydopamine-induced cell death in SH-SY5Y cells.
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.
Bando
Yoshio
Y
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan. ybando@asahikawa-med.ac.jp
Katayama
Taiichi
T
Taniguchi
Manabu
M
Ishibashi
Tomohiko
T
Matsuo
Noriyuki
N
Ogawa
Satoshi
S
Tohyama
Masaya
M
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D051938:Munc18 Proteins; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D017874:Immediate-Early Proteins; D051938:Munc18 Proteins; D009498:Neurotoxins; D016376:Oligonucleotides, Antisense; C106568:Scfd1 protein, rat; D016627:Oxidopamine; D020169:Caspases; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine