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 journalArticle

26 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 H 2O 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

Fingerprint

Dual Specificity Phosphatase 1
Oxidative stress
Oxidative Stress
Phosphotransferases
Apoptosis
Cell death
Cell Death
Mitogen-Activated Protein Kinase Phosphatases
Dual-Specificity Phosphatases
Cells
Phosphorylation
Vanadates
Corrosion inhibitors
Mitogen-Activated Protein Kinases
Phosphoric Monoester Hydrolases
Hydrogen Peroxide
Small Interfering RNA
phosphatase-1 kinase
Neuroblastoma
Transfection

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

MKP-1 contributes to oxidative stress-induced apoptosis via inactivation of ERK1/2 in SH-SY5Y cells. / Kim, Gab Seok; Choi, Yoo Keum; Song, Sun Sook; Kim, Won-Ki; Han, Byung Hee.

In: Biochemical and Biophysical Research Communications, Vol. 338, No. 4, 30.12.2005, p. 1732-1738.

Research output: Contribution to journalArticle

Kim, Gab Seok ; Choi, Yoo Keum ; Song, Sun Sook ; Kim, Won-Ki ; Han, Byung Hee. / MKP-1 contributes to oxidative stress-induced apoptosis via inactivation of ERK1/2 in SH-SY5Y cells. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 338, No. 4. pp. 1732-1738.
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