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.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2005 Dec 30|
- Oxidative stress
- Ubiquitin-proteasome pathway
ASJC Scopus subject areas
- Molecular Biology