Journal article
Dominant-negative Jun N-terminal protein kinase (JNK-1) inhibits metabolic oxidative stress during glucose deprivation in a human breast carcinoma cell line
Free radical biology & medicine, Vol.28(4), pp.575-584
2000
DOI: 10.1016/S0891-5849(99)00267-1
PMID: 10719239
Abstract
Signal transduction pathways involved in glucose deprivation-induced oxidative stress were investigated in human breast carcinoma cells (MCF-7/ADR). In MCF-7/ADR, glucose deprivation-induced prolonged activation of c-Jun N-terminal kinase (JNK1) as well as cytotoxicity and the accumulation of oxidized glutathione. Glucose deprivation also caused significant increases in total glutathione, cysteine, γ-glutamylcysteine, and immunoreactive proteins corresponding to the catalytic as well as regulatory subunits of γ-glutamylcysteine synthetase, suggesting that the synthesis of glutathione increased as an adaptive response. Expression of a catalytically inactive dominant negative JNK1 in MCF-7/ADR inhibited glucose deprivation-induced cell death and the accumulation of oxidized glutathione as well as altered the duration of JNK activation from persistent (>2 h) to transient (30 min). In addition, stimulation of glutathione synthesis during glucose deprivation was not observed in cells expressing the highest levels of dominant negative protein. Finally, a linear dose response suppression of oxidized glutathione accumulation was noted for clones expressing increasing levels of dominant negative JNK1 during glucose deprivation. These results show that expression of a dominant negative JNK1 protein was capable of suppressing persistent JNK activation as well as oxidative stress and cytotoxicity caused by glucose deprivation in MCF-7/ADR. These findings support the hypothesis that JNK signaling pathways may control the expression of proteins contributing to cell death mediated by metabolic oxidative stress during glucose deprivation. Finally, these results support the concept that JNK signaling-induced shifts in oxidative metabolism may provide a general mechanism for understanding the diverse biological effects seen during the activation of JNK signaling cascades.
Details
- Title: Subtitle
- Dominant-negative Jun N-terminal protein kinase (JNK-1) inhibits metabolic oxidative stress during glucose deprivation in a human breast carcinoma cell line
- Creators
- Yong J Lee - William Beaumont HospitalSandra S Galoforo - William Beaumont HospitalJulia E Sim - Washington University in St. LouisLisa A Ridnour - Washington University in St. LouisJinah Choi - University of Southern CaliforniaHenry Jay Forman - University of Southern CaliforniaPeter M Corry - William Beaumont HospitalDouglas R Spitz - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.28(4), pp.575-584
- DOI
- 10.1016/S0891-5849(99)00267-1
- PMID
- 10719239
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2000
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984313082202771
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