Activation of caspase-3 and c-Jun NH2-terminal kinase signaling pathways involving heroin-induced neuronal apoptosis

被引：33
作者：
Lai, Bingquan
Pu, Hongwei [2 ]
Cao, Qinghua [3 ]
Jing, Hualan [1 ]
Liu, Xiaoshan [1 ]
机构：
[1] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Forens Sci, Guangzhou 510080, Guangdong, Peoples R China
[2] Xinjiang Med Univ, Dept Pathol, Urumqi 830054, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou 510080, Guangdong, Peoples R China
来源：
NEUROSCIENCE LETTERS | 2011年 / 502卷 / 03期
关键词：
Heroin; JNK pathway; Cerebellar granule cell; Apoptosis; CEREBELLAR GRANULE NEURONS; RAT CORTICAL-NEURONS; UP-REGULATION; SPONGIFORM LEUKOENCEPHALOPATHY; SYMPATHETIC NEURONS; GENE-EXPRESSION; LOW POTASSIUM; FAS LIGAND; PC12; CELLS; DEATH;
D O I：
10.1016/j.neulet.2011.07.046
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Heroin has been shown to cause spongiform leukoencephalopathy (SLE) in heroin addicts. In this study, we found that heroin could induce apoptosis of primary cultured cerebellar granule cells (CGC) and c-Jun N-terminal kinase (JNK) pathway is activated during CGCs apoptosis. Inhibiting JNK with a specific inhibitor, SP600125, reduced the levels of c-Jun phosphorylation and caspase-3 activation. We also showed that use the JNK inhibitor SP600125, caspase inhibitor z-VAD, or use SP600125 and z-VAD together significantly suppressed cell death induced by heroin. These results indicate that JNK pathway is an important mediator of the neurotoxic effects of heroin and inhibiting JNK activity may represent a new and effective strategy to treat heroin-induced SLE. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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收藏
页码：209 / 213
页数：5
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