کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3165265 | 1198828 | 2009 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Peroxiredoxin I plays a protective role against cisplatin cytotoxicity through mitogen activated kinase signals Peroxiredoxin I plays a protective role against cisplatin cytotoxicity through mitogen activated kinase signals](/preview/png/3165265.png)
SummaryThe anticancer agent cis-diamminedichloroplatinum (cisplatin) is a first-line chemotherapeutic agent for oral cancer. Cell exposure to cisplatin is associated with increased oxidative stress and post-translational changes in components of apoptosis pathways, including p38 Mitogen-activated protein kinase (MAPK), c-Jun-NH2-kinase (JNK), and extracellular signal-regulated kinase (ERK). Peroxiredoxin (Prx) I is an oxidative stress-inducible protein expressed in many tissues and important for reducing reactive oxygen species in vivo; however, whether Prx I helps protect cells from cisplatin injury is unknown. In this report, we examined the effects of Prx I on cell sensitivity to cisplatin-induced apoptosis. Mouse embryo fibroblasts (MEFs) derived from Prx I-deficient mice showed increased cisplatin-induced apoptosis compared with wild-type MEFs. Cisplatin treatment also led to increased activation of p38 MAPK and JNK, and reduced ERK phosphorylation in Prx I-deficient MEFs compared with wild-type MEFs. Furthermore, JNK- and ERK-specific inhibitors protected the Prx I-deficient MEFs from cisplatin-induced apoptosis, but Prx I-deficient MEFs remained more sensitive than wild-type MEFs when treated with a p38 MAPK-specific inhibitor. These findings indicate that Prx I modulates the cisplatin-evoked activation of MAPKs that lead to apoptosis, and Prx I may thus represent a useful target as a protective therapy against cisplatin cytotoxicity.
Journal: Oral Oncology - Volume 45, Issue 12, December 2009, Pages 1037–1043