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Glutathione S-transferases as antioxidant enzymes: small cell lung cancer (H69) cells transfected with hGSTA1 resist doxorubicin-induced apoptosis.

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.
AuthorsAbha Sharma, Brad Patrick, Jie Li, Rajendra Sharma, Prince V S Jeyabal, Prasada M R V Reddy, Sanjay Awasthi, Yogesh C Awasthi
JournalArchives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 452 Issue 2 Pg. 165-73 (Aug 15 2006) ISSN: 0003-9861 [Print] United States
PMID16890185 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antioxidants
  • Doxorubicin
  • GSTA1 protein, human
  • Glutathione Transferase
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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