MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress.
MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress.
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DOI：
10.1007/s00210-011-0660-8
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发表时间：
2011-08
影响因子：
3.6
通讯作者：
Teismann, Peter
中科院分区：
文献类型：
--
作者：
Hsieh, Ya-Ching;Mounsey, Ross B.;Teismann, Peter
越来越多的证据表明，内源性多巴胺可能作为一种神经毒素参与帕金森病（PD）的病理生理。环氧合酶-2 （COX-2）由于其产生活性氧（ROS）的能力而与PD的发病机制有关。抑制COX-2通过阻止多巴胺-醌的形成导致神经保护。在这项研究中，我们研究了多巴胺是否介导1-甲基-4-苯基吡啶（MPP+）诱导的原发性腹侧中脑（VM）神经元（PD体外模型）的毒性，如果是，COX-2抑制剂对多巴胺介导的MPP+诱导的VM神经毒性和VM多巴胺能细胞凋亡的保护作用是否来自ROS的减少。多巴胺消耗剂利血平可显著降低MPP+诱导的VM神经毒性，而多巴胺对MPP+诱导的VM神经毒性和VM多巴胺能细胞凋亡具有累加作用。然而，选择性COX-2抑制剂（DFU）或布洛芬抑制COX-2可显著减弱MPP+诱导的VM细胞毒性和VM多巴胺能细胞凋亡，并伴有VM多巴胺能神经元中ROS生成的减少。这些结果表明，在COX-2存在下，多巴胺本身介导MPP+诱导的VM神经毒性和VM多巴胺能细胞凋亡。
Accumulating evidence suggests that endogenous dopamine may act as a neurotoxin and thereby participate in the pathophysiology of Parkinson’s disease (PD). Cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of PD due to its ability to generate reactive oxygen species (ROS). Inhibition of COX-2 leads to neuroprotection by preventing the formation of dopamine-quinone. In this study, we examined whether dopamine mediates 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in primary ventral mesencephalic (VM) neurons, an in vitro model of PD, and if so, whether the protective effects of COX-2 inhibitors on dopamine mediated MPP+-induced VM neurotoxicity and VM dopaminergic cell apoptosis result from the reduction of ROS. Reserpine, a dopamine-depleting agent, significantly reduced VM neurotoxicity induced by MPP+, whereas dopamine had an additive effect on MPP+-induced VM neurotoxicity and VM dopaminergic cell apoptosis. However, inhibition of COX-2 by a selective COX-2 inhibitor (DFU) or ibuprofen significantly attenuated MPP+-induced VM cell toxicity and VM dopaminergic cell apoptosis, which was accompanied by a decrease in ROS production in VM dopaminergic neurons. These results suggest that dopamine itself mediates MPP+-induced VM neurotoxicity and VM dopaminergic cell apoptosis in the presence of COX-2.
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影响因子：
3.5
作者：
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通讯作者：
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