Alteration of NRSF expression exacerbating 1-methyl-4-phenyl-pyridinium ion-induced cell death of SH-SY5Y cells

Neurosci Res. 2009 Nov;65(3):236-44. doi: 10.1016/j.neures.2009.07.006. Epub 2009 Jul 22.


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(+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Herbicides / toxicity
  • Humans
  • Models, Biological
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / physiopathology
  • RNA Interference
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Substantia Nigra / physiopathology


  • Herbicides
  • RE1-silencing transcription factor
  • RNA, Messenger
  • Repressor Proteins
  • 1-Methyl-4-phenylpyridinium