Specific up-regulation of GADD153/CHOP in 1-methyl-4-phenyl-pyridinium-treated SH-SY5Y cells

J Neurosci Res. 2002 Jun 15;68(6):755-60. doi: 10.1002/jnr.10252.

Abstract

Growth arrest DNA damage-inducible 153 (GADD153) expression was increased in 1-methyl-4-phenyl-pyridinium (MPP(+))-treated human SH-SY5Y neuroblastoma cells as determined by gene microarray analysis. GADD153 expression increased after 24 hr of MPP(+) (1 mM) exposure and preceded activation of caspase 3. Comparison of GADD153 expression among cultures treated with other toxins whose primary mode of action is either via mitochondrial impairment (rotenone) or via oxidative stress (6-hydroxydopamine or hydrogen peroxide) showed that GADD153 was uniquely up-regulated by MPP(+). Together these data suggest that a cellular mechanism distinct from mitochondrial impairment or oxidative stress contributes significantly to the up-regulation of GADD153 by MPP(+) and that GADD153 may function as an inducer of apoptosis following MPP(+) exposure. Published 2002 Wiley-Liss, Inc.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenylpyridinium / pharmacology*
  • 1-Methyl-4-phenylpyridinium / toxicity
  • Adrenergic Agents / pharmacology
  • Adrenergic Agents / toxicity
  • Blotting, Western
  • CCAAT-Enhancer-Binding Proteins / analysis*
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Caspase 3
  • Caspases / metabolism*
  • Enzyme Activation / drug effects
  • Herbicides / pharmacology*
  • Herbicides / toxicity
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Hydrogen Peroxide / toxicity
  • Insecticides / pharmacology
  • Insecticides / toxicity
  • Neuroblastoma
  • Oligonucleotide Array Sequence Analysis
  • Oxidants / pharmacology
  • Oxidants / toxicity
  • Oxidopamine / pharmacology
  • Oxidopamine / toxicity
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Rotenone / pharmacology
  • Rotenone / toxicity
  • Transcription Factor CHOP
  • Transcription Factors / analysis*
  • Transcription Factors / genetics
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • Adrenergic Agents
  • CCAAT-Enhancer-Binding Proteins
  • DDIT3 protein, human
  • Herbicides
  • Insecticides
  • Oxidants
  • RNA, Messenger
  • Transcription Factors
  • Rotenone
  • Transcription Factor CHOP
  • Oxidopamine
  • Hydrogen Peroxide
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • 1-Methyl-4-phenylpyridinium