Role of glutathione S-transferases in protection against lipid peroxidation. Overexpression of hGSTA2-2 in K562 cells protects against hydrogen peroxide-induced apoptosis and inhibits JNK and caspase 3 activation
| Autor: | Y, Yang, J Z, Cheng, S S, Singhal, M, Saini, U, Pandya, S, Awasthi, Y C, Awasthi |
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| Rok vydání: | 2001 |
| Předmět: |
DNA
Complementary Erythrocytes Time Factors MAP Kinase Kinase 4 Blotting Western Apoptosis Transfection Thiobarbituric Acid Reactive Substances Substrate Specificity In Situ Nick-End Labeling Humans Protein Isoforms Tissue Distribution Glutathione Transferase Mitogen-Activated Protein Kinase Kinases Caspase 3 Cell Membrane JNK Mitogen-Activated Protein Kinases DNA Hydrogen Peroxide Lipid Metabolism Precipitin Tests Enzyme Activation Oxygen Kinetics Oxidative Stress Caspases Electrophoresis Polyacrylamide Gel K562 Cells Protein Binding |
| Zdroj: | The Journal of biological chemistry. 276(22) |
| ISSN: | 0021-9258 |
| Popis: | The physiological significance of the selenium-independent glutathione peroxidase (GPx) activity of glutathione S-transferases (GSTs), associated with the major Alpha class isoenzymes hGSTA1-1 and hGSTA2-2, is not known. In the present studies we demonstrate that these isoenzymes show high GPx activity toward phospholipid hydroperoxides (PL-OOH) and they can catalyze GSH-dependent reduction of PL-OOH in situ in biological membranes. A major portion of GPx activity of human liver and testis toward phosphatidylcholine hydroperoxide (PC-OOH) is contributed by the Alpha class GSTs. Overexpression of hGSTA2-2 in K562 cells attenuates lipid peroxidation under normal conditions as well as during the oxidative stress and confers about 1.5-fold resistance to these cells from H(2)O(2) cytotoxicity. Treatment with 30 microm H(2)O(2) for 48 h or 40 microm PC-OOH for 8 h causes apoptosis in control cells, whereas hGSTA2-2-overexpressing cells are protected from apoptosis under these conditions. In control cells, H(2)O(2) treatment causes an early (within 2 h), robust, and persistent (at least 24 h) activation of JNK, whereas in hGSTA2-2-overexpressing cells, only a slight activation of JNK activity is observed at 6 h which declines to basal levels within 24 h. Caspase 3-mediated poly(ADP-ribose) polymerase cleavage is also inhibited in cells overexpressing hGSTA2-2. hGSTA2 transfection does not affect the function of antioxidant enzymes including GPx activity toward H(2)O(2) suggesting that the Alpha class GSTs play an important role in regulation of the intracellular concentrations of the lipid peroxidation products that may be involved in the signaling mechanisms of apoptosis. |
| Databáze: | OpenAIRE |
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