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 language | English |
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Pages (from-to) | 1732-1738 |
Number of pages | 7 |
Journal | Biochemical and biophysical research communications |
Volume | 338 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2005 Dec 30 |
Externally published | Yes |
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