RA410/Sly1 suppresses MPP+ and 6-hydroxydopamine-induced cell death in SH-SY5Y cells

被引：20

作者：

Bando, Y

Katayama, T

Taniguchi, M

Ishibashi, T

Matsuo, N

Ogawa, S

Tohyama, M

机构：

[1] Osaka Univ, Grad Sch Med, Dept Anat & Neurosci, Osaka 5650871, Japan

[2] CREST, JST, Kawaguchi, Japan

[3] Dainippon Pharmaceut Co Ltd, Licensing Div, Osaka, Japan

[4] Kanazawa Univ, Sch Med, Dept Neuroanat, Kanazawa, Ishikawa, Japan

来源：

NEUROBIOLOGY OF DISEASE | 2005年 / 18卷 / 01期

基金：

日本科学技术振兴机构;

关键词：

Parkinson's disease; vesicle transport; MPP; 6-OHDA and cell death;

D O I：

10.1016/j.nbd.2004.09.008

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

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 wildtype 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. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：143 / 151

页数：9

共 51 条

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GRP94 (94 kDa glucose-regulated protein) suppresses ischemic neuronal cell death against ischemia/reperfusion injury [J].