Journal article
Protective role of Bcl2 in metabolic oxidative stress-induced cell death
Journal of cell science, Vol.114(4), pp.677-684
02/15/2001
DOI: 10.1242/jcs.114.4.677
PMID: 11171373
Abstract
Previous studies have shown that overexpression of Bcl2 protects cells from glucose deprivation-induced cell death in multidrug-resistant human breast carcinoma, MCF-7/ADR cells. In this study, we further investigated the protective role of Bcl2 in glucose deprivation-induced cytotoxicity. Although Bcl2 did not prevent a 3.2-fold increase in the level of hydroperoxide during glucose deprivation, it led to a compartmentalization of hydroperoxide molecules in the mitochondria. It also inhibited glucose deprivation-induced cytochrome c release from the mitochondria. It is possible that overexpression of Bcl2 prevents glucose deprivation-induced ceramide generation, probably by preventing the leakage of hydroperoxide from the mitochondria. We also observed that glucose deprivation induced a sixfold increase in oxidized glutathione content, as well as in thiol precursor content. Overexpression of Bcl2 suppressed an increase in oxidized glutathione content and thiol precursor content. Our results indicate that Bcl2 protects cells from metabolic oxidative stress-induced damage by inhibiting the leakage of hydroperoxide from the mitochondria and subsequently preventing ceramide generation. Preventing ceramide generation inhibits the signal transduction pathway and results in the suppression of cytochrome c release from the mitochondria.
Details
- Title: Subtitle
- Protective role of Bcl2 in metabolic oxidative stress-induced cell death
- Creators
- Yong J Lee - UPMC Hillman Cancer CenterJenn C. Chen - UPMC Hillman Cancer CenterAndrew A Amoscato - University of Pittsburgh Cancer InstituteJaafar Bennouna - University of Pittsburgh Cancer InstituteDouglas R Spitz - UPMC Hillman Cancer CenterMohan Suntharalingam - University of Pittsburgh Cancer InstituteJuong G Rhee - University of Pittsburgh Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.114(4), pp.677-684
- DOI
- 10.1242/jcs.114.4.677
- PMID
- 11171373
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Language
- English
- Date published
- 02/15/2001
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984313079402771
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