Role of GST P1-1 in mediating the effect of etoposide on human neuroblastoma cell line Sh-Sy5y

✍ Scribed by S. Bernardini; L. Bellincampi; S. Ballerini; M. Ranalli; A. Pastore; C. Cortese; G. Federici

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 150 KB
• Volume: 86
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10219

✦ Synopsis

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.