Glucose Deprivation-induced Cytotoxicity and Alterations in Mitogen-activated Protein Kinase Activation Are Mediated by Oxidative Stress in Multidrug-resistant Human Breast Carcinoma Cells

Yong J. Lee; Sandra S. Galoforo; Christine M. Berns; Jenn C. Chen; Bruce H. Davis; Julia E. Sim; Peter M. Corry; Douglas R. Spitz

doi:10.1074/jbc.273.9.5294

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Glucose Deprivation-induced Cytotoxicity and Alterations in Mitogen-activated Protein Kinase Activation Are Mediated by Oxidative Stress in Multidrug-resistant Human Breast Carcinoma Cells

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Glucose Deprivation-induced Cytotoxicity and Alterations in Mitogen-activated Protein Kinase Activation Are Mediated by Oxidative Stress in Multidrug-resistant Human Breast Carcinoma Cells

Yong J. Lee, Sandra S. Galoforo, Christine M. Berns, Jenn C. Chen, Bruce H. Davis, Julia E. Sim, Peter M. Corry and Douglas R. Spitz

The Journal of biological chemistry, Vol.273(9), pp.5294-5299

02/1998

DOI: 10.1074/jbc.273.9.5294

PMID: 9478987

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Abstract

We previously observed that glucose deprivation induces cell death in multidrug-resistant human breast carcinoma cells (MCF-7/ADR). As a follow up we wished to test the hypothesis that metabolic oxidative stress was the causative process or at least the link between causative processes behind the cytotoxicity. In the studies described here, we demonstrate that mitogen-activated protein kinase (MAPK) was activated within 3 min of being in glucose-free medium and remained activated for 3 h. Glucose deprivation for 2–4 h also caused oxidative stress as evidenced by a 3-fold greater steady state concentration of oxidized glutathione and a 3-fold increase in pro-oxidant production. Glucose and glutamate treatment rapidly suppressed MAPK activation and rescued cells from cytotoxicity. Glutamate and the peroxide scavenger, pyruvate, rescued the cells from cell killing as well as suppressed pro-oxidant production. In addition the thiol antioxidant, N-acetyl-l-cysteine, rescued cells from glucose deprivation-induced cytotoxicity and suppressed MAPK activation. These results suggest that glucose deprivation-induced cytotoxicity and alterations in MAPK signal transduction are mediated by oxidative stress in MCF-7/ADR. These results also support the speculation that a common mechanism of glucose deprivation-induced cytotoxicity in mammalian cells may involve metabolic oxidative stress.

Details

Title: Subtitle: Glucose Deprivation-induced Cytotoxicity and Alterations in Mitogen-activated Protein Kinase Activation Are Mediated by Oxidative Stress in Multidrug-resistant Human Breast Carcinoma Cells
Creators: Yong J. Lee - Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073
Sandra S. Galoforo - Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073
Christine M. Berns - Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073
Jenn C. Chen - Department of Clinical Pathology William Beaumont Hospital Royal Oak, Michigan 48073
Bruce H. Davis - Department of Clinical Pathology William Beaumont Hospital Royal Oak, Michigan 48073
Julia E. Sim - Washington University in St. Louis
Peter M. Corry - Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073
Douglas R. Spitz - Washington University in St. Louis
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.273(9), pp.5294-5299
DOI: 10.1074/jbc.273.9.5294
PMID: 9478987
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Language: English
Date published: 02/1998
Academic Unit: Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984312974002771

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