Journal article
Mitochondrial O2⋅¯ and H2O2 Mediate Glucose Deprivation-induced Stress in Human Cancer Cells
The Journal of biological chemistry, Vol.280(6), pp.4254-4263
02/11/2005
DOI: 10.1074/jbc.M411662200
PMID: 15561720
Abstract
The hypothesis that glucose deprivation-induced cytotoxicity in transformed human cells is mediated by mitochondrial O2⋅¯ and H2O2 was first tested by exposing glucose-deprived SV40-transformed human fibroblasts (GM00637G) to electron transport chain blockers (ETCBs) known to increase mitochondrial O2⋅¯ and H2O2 production (antimycin A (AntA), myxothiazol (Myx), or rotenone (Rot)). Glucose deprivation (2–8 h) in the presence of ETCBs enhanced parameters indicative of oxidative stress (i.e. GSSG and steady-state levels of oxygen-centered radicals) as well as cytotoxicity. Glucose deprivation in the presence of AntA also significantly enhanced cytotoxicity and parameters indicative of oxidative stress in several different human cancer cell lines (PC-3, DU145, MDA-MB231, and HT-29). In addition, human osteosarcoma cells lacking functional mitochondrial electron transport chains (rho(0)) were resistant to glucose deprivation-induced cytotoxicity and oxidative stress in the presence of AntA. In the absence of ETCBs, aminotriazole-mediated inactivation of catalase in PC-3 cells demonstrated increases in intracellular steady-state levels of H2O2 during glucose deprivation. Finally, in the absence of ETCBs, overexpression of manganese containing superoxide dismutase and/or mitochondrial targeted catalase using adenoviral vectors significantly protected PC-3 cells from toxicity and oxidative stress induced by glucose deprivation with expression of both enzymes providing greater protection than was seen with either alone. Overall, these findings strongly support the hypothesis that mitochondrial O2⋅¯ and H2O2 significantly contribute to glucose deprivation-induced cytotoxicity and metabolic oxidative stress in human cancer cells.
Details
- Title: Subtitle
- Mitochondrial O2⋅¯ and H2O2 Mediate Glucose Deprivation-induced Stress in Human Cancer Cells
- Creators
- Iman M Ahmad - University of IowaNukhet Aykin-Burns - University of IowaJulia E Sim - Washington University in St. LouisSusan A Walsh - University of IowaRyuji Higashikubo - Washington University in St. LouisGarry R Buettner - University of IowaSujatha Venkataraman - University of IowaMichael A Mackey - University of IowaShawn W Flanagan - University of IowaLarry W Oberley - University of IowaDouglas R Spitz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.280(6), pp.4254-4263
- DOI
- 10.1074/jbc.M411662200
- PMID
- 15561720
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 02/11/2005
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
- Record Identifier
- 9984197133602771
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