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

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• 作者：Abha Sharma ; Brad Patrick ; Jie Li ; Rajendra Sharma ; Prince V.S. Jeyabal ; Prasada M.R.V. Reddy ; Sanjay Awasthi and Yogesh C. Awasthi
• 关键词：Glutathione S-transferases ; Glutathione ; Lipid peroxidation ; Small cell lung cancer ; Doxorubicin ; Apoptosis
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：2006
• 出版时间：15 August 2006
• 年：2006
• 卷：452
• 期：2
• 页码：165-173
• 全文大小：722 K

文摘

It has been suggested that the α-class glutathione S-transferases (GSTs) protect various cell types from oxidative stress and lipid peroxidation (LPO). In order to examine the protective role of α-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 α-class GSTs provide protection against oxidative stress by attenuating lipid peroxidation and these enzymes can modulate signaling for apoptosis.