期刊
JOURNAL OF PINEAL RESEARCH
卷 46, 期 1, 页码 64-70出版社
WILEY
DOI: 10.1111/j.1600-079X.2008.00629.x
关键词
arsenite; dorsal root ganglion explants; endoplasmic reticulum stress; melatonin; mitochondria; neurotoxicity
资金
- University of Colorado Health Sciences Center, Aurora, CO, USA [NSC96-2320-B-010-023, VGH97-373]
In this study, the effect of melatonin on sodium arsenite (arsenite)-induced peripheral neurotoxicity was investigated using dorsal root ganglion (DRG) explants. After 24-hr incubation, arsenite (30 mu m) consistently elevated the expression of heat shock protein 70 and haeme oxygenase-1, two well-known stress proteins, in the treated DRG explants. Co-incubation with melatonin (4 and 20 mm) concentration-dependently attenuated arsenite-induced elevation in stress proteins. Furthermore, melatonin inhibited arsenite-induced phosphorylation of p38 and DNA fragmentation. Inhibition by melatonin of arsenite-induced apoptosis was mediated via inactivating both endoplasmic reticulum (ER) and mitochondrial pathways. In the ER pathway, melatonin suppressed arsenite-induced elevation in activating transcription factor-6 and CCAAT/enhancer-binding protein homologous protein in the nuclear fraction of the treated DRG explants. Moreover, melatonin attenuated arsenite-induced activation of caspase 12, an ER-specific enzyme. In the mitochondrial pathway, arsenite-induced increases in Bcl-2 levels and cytosolic cytochrome c were reduced by melatonin. At the same time, melatonin inhibited arsenite-induced activation of caspase 3 in the treated DRG explants. Compared with glutathione and N-acetyl cysteine, melatonin was more potent than either in inhibiting arsenite-induced elevation in stress proteins. Taken together, our study demonstrates that melatonin is protective against arsenite-induced neurotoxicity in DRG explants. In addition, melatonin prevented arsenite-induced apoptosis via suppression of ER and mitochondrial activation. Our data suggest that melatonin is potentially a therapy for arsenite-induced peripheral neuropathy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据