Alteration of NRSF expression exacerbating 1-methyl-4-phenyl-pyridinium ion-induced cell death of SH-SY5Y cells.
Neuron-restrictive silencer factor (NRSF)/neuronal repressor element-1 silencing transcription factor (REST) and its neuron-specific truncated form REST4 participates in the pathological processes of nervous system diseases, such as global ischemia, epilepsy, Huntington disease and so on. In this paper, we investigated the changes of NRSF and REST4 in a cellular model of Parkinson's disease (PD). Our results showed that neurotoxin 1-methyl-4-phenyl-pyridinium ion (MPP(+)) treatment triggered the mRNA and protein expression of NRSF and REST4, and caused both NRSF and REST4 proteins relocalized between the nucleus and cytoplasm in human dopaminergic SH-SY5Y cells. Redistribution of NRSF and REST4 derepressed the expression of target genes at late time points. Furthermore, alteration of NRSF and REST4 expression by overexpression or RNAi techniques elicited deleterious effects on cell viability of SH-SY5Y treated with toxic MPP(+).
Yu
Mei
M
National Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Cai
Lei
L
Liang
Min
M
Huang
Yalin
Y
Gao
Hui
H
Lu
Shiduo
S
Fei
Jian
J
Huang
Fang
F
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D008954:Models, Biological; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000099229:RE1-Silencing Transcription Factor
D015655:1-Methyl-4-phenylpyridinium; D006540:Herbicides; D012333:RNA, Messenger; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor