title: Inhibition of alpha7-nicotinic acetylcholine receptor expression by arsenite in the vascular endothelial cells.
abstract: The alpha7-nicotinic acetylcholine receptor (alpha7-nAChR), expressed in the neuronal and non-neuronal cells, has been shown to regulate cell proliferation. However, the expression and function of the alpha7-nAChR in the proliferation of the vascular endothelial cells remain unclear. In this study, we investigated the expression of the alpha7-nAChR in the arsenite-exposed vascular endothelial cells. The vascular endothelial cells SVEC4-10 and porcine aorta endothelial cells (PAEC) expressed the alpha7-nAChR proteins. Moreover, the location of the alpha7-nAChR proteins on cell membrane of the vascular endothelial cells was identified by the alpha7-nAChR binding to a tetramethylrhodamine-labeled alpha-bungarotoxin (alpha-BTX). Arsenite (20 microM, 24 h) significantly induced the cytotoxicity, cell growth inhibition, and apoptosis in the vascular endothelial cells. The level of alpha7-nAChR proteins was concentration dependently decreased in the arsenite-treated endothelial cells. Furthermore, a specific alpha7-nAChR antagonist, alpha-BTX, inhibited the cell viability in the vascular endothelial cells. Nevertheless, alpha-BTX, and a alpha7-nAChR agonist, nicotine, did not significantly alter the cytotoxicity in the arsenite-treated endothelial cells. In addition, arsenite decreased the level of endothelial nitric oxide synthase proteins but did not alter choline acetyltransferase proteins in the SVEC4-10 endothelial cells. Together, our results indicate that arsenite can inhibit the alpha7-nAChR protein expression and cause the cell injury in the vascular endothelial cells.
authors.affiliation: Molecular Toxicology Laboratory, Institute of Pharmacology and Toxicology, College of Life Sciences, Tzu Chi University, 701 Section 3, Hualien 970, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Hsu
authors.forename: Tsui-Chun
authors.initials: TC
authors.lastname: Tsou
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Chiu
authors.forename: Jui-I
authors.initials: JI
authors.lastname: Chao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000494:pharmacology*; D015153:Blotting, Western; D002038:Bungarotoxins / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018733:Nicotinic Antagonists; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D016716:PC12 Cells; D051381:Rats; D011978:Receptors, Nicotinic / Q000096:biosynthesis*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D018053:Arsenites; D002038:Bungarotoxins; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D002795:Choline O-Acetyltransferase; C015001:arsenite