Journal article
Glutathione S-transferase p elicits protection against H2O2-induced cell death via coordinated regulation of stress kinases
Cancer research (Chicago, Ill.), Vol.60(15), pp.4053-4057
2000
PMID: 10945608
Abstract
To elucidate mechanisms underlying glutathione S-transferase p (GSTp)-mediated cellular protection against oxidative stress-induced cell death, the effect of GSTp on stress signaling pathways was investigated before and after H2O2 treatment. Under nonstressed conditions, increased expression of GSTp via a tet-off-inducible GSTp in NIH 3T3 cells increased the phosphorylation of mitogen-activated protein (MAP) kinase kinase 4, p38, extracellular receptor kinase (ERK), and inhibitor of kappa-kinase (IKK), and reduced phosphorylation of MAP kinase kinase 7 and Jun NH2-terminal kinase (JNK). Whereas H2O2 treatment of cells induced JNK, p38, and IKK activities, in the presence of H2O2 and elevated GSTp expression there was an additional increase in ERK, p38, and IKK activities and a decrease in JNK activity. GSTp-mediated protection from H2O2-induced death was attenuated upon inhibition of p38, nuclear factor KB, or MAP kinase by dominant negative or pharmacological inhibitors. Conversely, expression of a dominant negative JNK protected cells from H2O2-mediated death. These data suggest that the coordinated regulation of stress kinases by GSTp, as reflected by increased p38, ERK, and nuclear factor kappaB activities together with suppression of JNK signaling, contributes to protection of cells against reactive oxygen species-mediated death.
Details
- Title: Subtitle
- Glutathione S-transferase p elicits protection against H2O2-induced cell death via coordinated regulation of stress kinases
- Creators
- Zhimin Yin - Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, United StatesV. N IVANOV - Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, United StatesH HABELHAH - Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, United StatesK TEW - Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, United StatesZ RONAI - Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.60(15), pp.4053-4057
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- PMID
- 10945608
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2000
- Academic Unit
- Pathology
- Record Identifier
- 9984047618102771
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