Aim Alpha7 nicotinic acetylcholine receptor (a7nAChR), 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 o7nAChR on oxidant stressinduced injury in endothelial cells.Methods Cultured human umbilical vein endothelial cells were treated with H202 (400 μmol · L1)or H2O2plus PNU282987 (10 μmol · L1).Cell viability and membrane integrity were measured.AnnexinV + PI assay, immunoblotting of bcl2, bax and cleaved caspase3, and immunofluorescence of apoptosis inducing factor(AIF) were performed to evaluate apoptosis.Protein expression of vascular peroxidase1 (VPO1) and phosphorJNK were measured by immunoblotting.Results Activation of α7nAChR by a selective agonist PNU282987 prevented H2O2indced decrease of cell viability and increase of lactate dehydrogenase release.Activation of 7nAChR markedly reduced cell apoptosis and intracellular oxidative stress level.Moreover, activation of oα7nAChR reduced H2O2induced VPO1 protein upregulation and JNK1/2 phosphorylation.The inhibitory effect of α7nAChR activation on VPO1 was blocked by JNK inhibitor SP600125.In addition, pretreatment of α7nAChR antagonist methyllycaconitine blocked the cytoprotective effect of PNU282987.Conclusion These results provide the first evidence that activation of α7nAChR protects against oxidant stressinduced damage by suppressing VPO1 in a JNK signaling pathwaydependent manner in endothelial cells.