Activation of α7 Nicotinic Acetylcholine Receptor Protects Against Oxidant Stress Damage Through Reducing Vascular Peroxidase-1 in a JNK Signaling-Dependent Manner in Endothelial Cells
Activation of α7 Nicotinic Acetylcholine Receptor Protects Against Oxidant Stress Damage Through Reducing Vascular Peroxidase-1 in a JNK Signaling-Dependent Manner in Endothelial Cells
复制标题
α7 烟碱乙酰胆碱受体的激活通过在内皮细胞中以 JNK 信号传导依赖性方式减少血管过氧化物酶 1 来防止氧化应激损伤
DOI：
10.1159/000358627
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发表时间：
2014-01-01
影响因子：
--
通讯作者：
Shen, Fu-Ming
中科院分区：
文献类型：
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作者：
Li, Dong-Jie;Zhao, Ting;Shen, Fu-Ming
Aim: Alpha7 nicotinic acetylcholine receptor (alpha 7nAChR), a subtype of nAChR regulating neurotransmission in central nervous system, is an essential regulator of cholinergic antiinflammatory pathway in periphery. The present study was to determine the effects of activation of alpha 7nAChR on oxidant stress-induced injury in endothelial cells. Methods: Cultured human umbilical vein endothelial cells were treated with H2O2 (400 mu M) or H2O2 plus PNU-282987 (10 mu M). Cell viability and membrane integrity were measured. Annexin V + PI assay, immunoblotting of bcl-2, bax and cleaved capase-3, and immunofluorescence of apoptosis inducing factor (AIF) were performed to evaluate apoptosis. Protein expression of vascular peroxidase-1 (VPO-1) and phosphor-JNK were measured by immunoblotting. Results: Activation of alpha 7nAChR by a selective agonist PNU-282987 prevented H2O2-indced decrease of cell viability and increase of lactate dehydrogenase release. Activation of alpha 7nAChR markedly reduced cell apoptosis and intracellular oxidative stress level. Moreover, activation of alpha 7nAChR reduced H2O2-induced VPO-1 protein upregulation and JNK1/2 phosphorylation. The inhibitory effect of alpha 7nAChR activation on VPO-1 was blocked by JNK inhibitor SP600125. In addition, pretreatment of alpha 7nAChR antagonist methyllycaconitine blocked the cytoprotective effect of PNU-282987. Conclusion: These results provide the first evidence that activation of alpha 7nAChR protects against oxidant stress-induced damage by suppressing VPO-1 in a JNK signaling pathway-dependent manner in endothelial cells. Copyright (C) 2014 S. Karger AG, Basel
