Abstract |
It has been suggested that the alpha-class glutathione S- transferases ( GSTs) protect various cell types from oxidative stress and lipid peroxidation (LPO). In order to examine the protective role of alpha-class GST isozyme hGSTA1-1 against doxorubicin (DOX)-induced lipid peroxidation, cytotoxicity, and apoptosis, human small cell lung cancer (SCLC) H69 cells were stably transfected with hGSTA1. Immunological and biochemical characterization of hGSTA1-transfected cells revealed the expression of functionally active hGSTA1-1 localized near the cellular plasma membranes. hGSTA1-transfected cells acquired significantly increased resistance to the DOX-induced cytotoxicity by suppressing lipid peroxidation levels in these cells. Overexpression of hGSTA1-1 in cells inhibited DOX-mediated depletion of GSH and higher GSH levels were found in DOX-treated hGSTA1-transfected cells as compared with empty vector-transfected controls. hGSTA1-1 overexpression also provided protection to cells from DOX-induced apoptosis by inhibiting phosphorylation of c-Jun-N-terminal kinases (JNK), caspase-3 activation, and by preserving the levels of anti-apoptotic protein Bcl-2. These results are consistent with the idea that the alpha-class GSTs provide protection against oxidative stress by attenuating lipid peroxidation and these enzymes can modulate signaling for apoptosis.
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Authors | Abha Sharma, Brad Patrick, Jie Li, Rajendra Sharma, Prince V S Jeyabal, Prasada M R V Reddy, Sanjay Awasthi, Yogesh C Awasthi |
Journal | Archives of biochemistry and biophysics
(Arch Biochem Biophys)
Vol. 452
Issue 2
Pg. 165-73
(Aug 15 2006)
ISSN: 0003-9861 [Print] United States |
PMID | 16890185
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antioxidants
- Doxorubicin
- GSTA1 protein, human
- Glutathione Transferase
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Topics |
- Antioxidants
(metabolism)
- Apoptosis
(drug effects)
- Carcinoma, Small Cell
(enzymology, genetics, pathology)
- Cell Line, Tumor
- Doxorubicin
(administration & dosage)
- Glutathione Transferase
(genetics, metabolism)
- Humans
- Transfection
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