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

doi:10.1016/j.bbrc.2005.10.143

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 journal › Article › peer-review

30 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 language	English
Pages (from-to)	1732-1738
Number of pages	7
Journal	Biochemical and biophysical research communications
Volume	338
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2005.10.143
Publication status	Published - 2005 Dec 30
Externally published	Yes

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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10.1016/j.bbrc.2005.10.143

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

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.",

keywords = "Apoptosis, Caspase-3, ERK1/2, MKP-1, Neurons, Oxidative stress, Phosphatases, Ubiquitin-proteasome pathway, siRNA",

author = "Kim, {Gab Seok} and Choi, {Yoo Keum} and Song, {Sun Sook} and Kim, {Won Ki} and Han, {Byung Hee}",

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.",

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AU - Kim, Gab Seok

AU - Choi, Yoo Keum

AU - Song, Sun Sook

AU - Kim, Won Ki

AU - Han, Byung Hee

N1 - 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.

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 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.

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 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.

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KW - MKP-1

KW - Neurons

KW - Oxidative stress

KW - Phosphatases

KW - Ubiquitin-proteasome pathway

KW - siRNA

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ER -

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

Abstract

Bibliographical note

Keywords

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