Involvement of oxidative stress-activated JNK signaling in the methamphetamine-induced cell death of human SH-SY5Y cells

Sheng Fan Wang, Jiin Cherng Yen, Pen Hui Yin, Chin Wen Chi, Hsin Chen Lee*

*此作品的通信作者

研究成果: Article同行評審

67 引文 斯高帕斯(Scopus)

摘要

Methamphetamine (METH) is one of the most commonly abused drugs that may result in neurotoxic damage. Many lines of evidence have revealed that oxidative stress plays an important role in METH-induced neurotoxic effects. In a previous study, it was demonstrated in human neuroblastoma SH-SY5Y cells that enhanced oxidative stress was related to METH-induced apoptosis. To evaluate which of the three major mitogen-activated protein (MAP) kinase signaling pathways are involved in the process, namely the extracellular signal-related kinases (ERK), the p38 MAP kinases (p38) and the Jun-N-terminal kinases (JNK), we performed a time-course assessment. This indicated that METH induced an increase in the phosphorylation of ERK and JNK, but not of p38. Moreover, a JNK-specific inhibitor, SP600125, partially but significantly rescued METH-induced cell death, while PD98059 (an ERK kinase inhibitor) and SB203580 (a p38 inhibitor) had no protective effect. We also found that vitamin E (Vit E) prevented METH-induced JNK phosporylation and SP600125 inhibited METH-induced c-Jun phosphorylation. Furthermore, METH-activated caspase-3 activity was significantly repressed by Vit E and in SP600125 treated cells. We suggest that the oxidative stress-activated JNK signaling pathway is involved in METH-induced cell death.

原文English
頁(從 - 到)234-241
頁數8
期刊Toxicology
246
發行號2-3
DOIs
出版狀態Published - 18 4月 2008

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