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 language | English |
|---|---|
| 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 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - MKP-1 contributes to oxidative stress-induced apoptosis via inactivation of ERK1/2 in SH-SY5Y cells
AU - Kim, Gab Seok
AU - Choi, Yoo Keum
AU - Song, Sun Sook
AU - Kim, Won-Ki
AU - Han, Byung Hee
PY - 2005/12/30
Y1 - 2005/12/30
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Caspase-3
KW - ERK1/2
KW - MKP-1
KW - Neurons
KW - Oxidative stress
KW - Phosphatases
KW - siRNA
KW - Ubiquitin-proteasome pathway
UR - http://www.scopus.com/inward/record.url?scp=27844477729&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27844477729&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.10.143
DO - 10.1016/j.bbrc.2005.10.143
M3 - Article
C2 - 16289033
AN - SCOPUS:27844477729
VL - 338
SP - 1732
EP - 1738
JO - The BMJ
JF - The BMJ
SN - 0730-6512
IS - 4
ER -