Role of GST P1-1 in mediating the effect of etoposide on human neuroblastoma cell line Sh-Sy5y.
The oxidative stress could have a dual action on glutathione S-transferase (GST) P1-1 metabolism: transcriptional induction and/or polymerization. The former should represent a form of adaptation to oxidative stress and contribute to protect the cell, the latter one should activate apoptosis via c-Jun N-terminal kinase (JNK). We studied the effect of etoposide on human neuroblastoma cell line SH-SY5Y and on an etoposide-resistant clone to investigate whether a pleiotropic effect of etoposide on the redox status of the cell exists which is able to interfere with apoptosis through the GST P1-1 system. Etoposide treatment was able to induce GST P1-1 polymerization and activation of apoptosis. The data obtained from our etoposide-resistant clone and the possibility to reverse the sensitive phenotype to a resistant one by means of hexyl-glutathione preincubation, seem to suggest that cellular levels of glutathione have a key role in protecting GST P1-1 by oxidation and consequently the cell's decision between life and death.
Department of Internal Medicine, University of Rome Tor Vergata, Italy. Bernardini@Med.UniRoma2.it
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Bernardini
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Bellincampi
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Ballerini
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Ranalli
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Pastore
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Cortese
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Federici
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D005047:Etoposide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D005978:Glutathione; C033550:hexylglutathione