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- Title
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.
- Authors
Li, Dong-Jie; Zhao, Ting; Xin, Ru-Juan; Wang, Yuan-Yuan; Fei, Yi-Bo; Shen, Fu-Ming
- Abstract
Aim: Alpha7 nicotinic acetylcholine receptor (α7nAChR), a subtype of nAChR regulating neurotransmission in central nervous system, is an essential regulator of cholinergic anti-inflammatory pathway in periphery. The present study was to determine the effects of activation of α7nAChR on oxidant stress-induced injury in endothelial cells. Methods: Cultured human umbilical vein endothelial cells were treated with H2O2 (400 µM) or H2O2 plus PNU-282987 (10 µM). 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 α7nAChR by a selective agonist PNU-282987 prevented H2O2-indced decrease of cell viability and increase of lactate dehydrogenase release. Activation of α7nAChR markedly reduced cell apoptosis and intracellular oxidative stress level. Moreover, activation of α7nAChR reduced H2O2-induced VPO-1 protein upregulation and JNK1/2 phosphorylation. The inhibitory effect of α7nAChR activation on VPO-1 was blocked by JNK inhibitor SP600125. In addition, pretreatment of α7nAChR antagonist methyllycaconitine blocked the cytoprotective effect of PNU-282987. Conclusion: These results provide the first evidence that activation of α7nAChR protects against oxidant stress-induced damage by suppressing VPO-1 in a JNK signaling pathway-dependent manner in endothelial cells. © 2014 S. Karger AG, Basel
- Subjects
NICOTINIC acetylcholine receptors; OXIDATIVE stress; PEROXIDASE; CELLULAR signal transduction; ENDOTHELIAL cells; NEURAL transmission; PARASYMPATHOMIMETIC agents; UMBILICAL veins
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2014, Vol 33, Issue 2, p468
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000358627