MKP-1 contributes to oxidative stress-induced apoptosis via inactivation of ERK1/2 in SH-SY5Y cells

Gab Seok Kim, Yoo Keum Choi, Sun Sook Song, Won Ki Kim, Byung Hee Han

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is a dual specificity phosphatase that negatively regulates the MAP kinases. In this study, we found that levels of MKP-1 expression were transiently decreased within 3 h, followed by an increase 6-9 h after H2O 2-induced oxidative stress in human neuroblastoma SH-SY5Y cells. There was a strong negative correlation between MKP-1 expression and ERK1/2 phosphorylation levels. Treatment of cells with a proteasomal inhibitor MG132 decreased the oxidative stress-induced degradation of MKP-1, resulting in dephosphorylation of ERK1/2. MG132 potentiated hydrogen peroxide-induced cell death, which was attenuated by a phosphatase inhibitor sodium orthovanadate. Suppression of MKP-1 expression by transfection with siRNA duplexes specific to MKP-1 transcript resulted in a decrease in oxidative stress-induced cell death. These data therefore suggest that MKP-1, a negative regulator of ERK1/2, plays a proapoptotic role in oxidative stress-induced cell death in a neuronal cell line.

Original languageEnglish
Pages (from-to)1732-1738
Number of pages7
JournalBiochemical and biophysical research communications
Volume338
Issue number4
DOIs
Publication statusPublished - 2005 Dec 30
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by Grant M103KV010005 04K2201 00530 (B.H.H.) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology and by a grant of Korea Health R&D Project (02-PJ1-PG3-21301-0004) by the Ministry of Health and Welfare, Republic of Korea.

Keywords

  • Apoptosis
  • Caspase-3
  • ERK1/2
  • MKP-1
  • Neurons
  • Oxidative stress
  • Phosphatases
  • Ubiquitin-proteasome pathway
  • siRNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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